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Sample records for affibody molecule labeled

  1. Evaluation of maleimide derivative of DOTA for site-specific labeling of recombinant affibody molecules.

    Science.gov (United States)

    Ahlgren, Sara; Orlova, Anna; Rosik, Daniel; Sandström, Mattias; Sjöberg, Anna; Baastrup, Barbro; Widmark, Olof; Fant, Gunilla; Feldwisch, Joachim; Tolmachev, Vladimir

    2008-01-01

    Affibody molecules are a new class of small (7 kDa) scaffold affinity proteins, which demonstrate promising properties as agents for in vivo radionuclide targeting. The Affibody scaffold is cysteine-free and therefore independent of disulfide bonds. Thus, a single thiol group can be engineered into the protein by introduction of one cysteine. Coupling of thiol-reactive bifunctional chelators can enable site-specific labeling of recombinantly produced Affibody molecules. In this study, the use of 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid-10-maleimidoethylacetamide (MMA-DOTA) for 111 In-labeling of anti-HER2 Affibody molecules His 6-Z HER2:342-Cys and Z HER2:2395-Cys has been evaluated. The introduction of a cysteine residue did not affect the affinity of the proteins, which was 29 pM for His 6-Z HER2:342-Cys and 27 pM for Z HER2:2395-Cys, comparable with 22 pM for the parental Z HER2:342. MMA-DOTA was conjugated to DTT-reduced Affibody molecules with a coupling efficiency of 93% using a 1:1 molar ratio of chelator to protein. The conjugates were labeled with 111 In to a specific radioactivity of up to 7 GBq/mmol, with preserved binding for the target HER2. In vivo, the non-His-tagged variant 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys demonstrated appreciably lower liver uptake than its His-tag-containing counterpart. In mice bearing HER2-expressing LS174T xenografts, 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys showed specific and rapid tumor localization, and rapid clearance from blood and nonspecific compartments, leading to a tumor-to-blood-ratio of 18 +/- 8 already 1 h p.i. Four hours p.i., the tumor-to-blood ratio was 138 +/- 8. Xenografts were clearly visualized already 1 h p.i. PMID:18163536

  2. Direct comparison of {sup 111}In-labelled two-helix and three-helix Affibody molecules for in vivo molecular imaging

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    Rosik, Daniel; Karlstroem, Amelie Eriksson [KTH Royal Institute of Technology, Division of Molecular Biotechnology, School of Biotechnology, Stockholm (Sweden); Orlova, Anna; Malmberg, Jennie; Varasteh, Zohreh [Uppsala University, Preclinical PET Platform, Uppsala (Sweden); Altai, Mohamed; Tolmachev, Vladimir [Uppsala University, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Sandstroem, Mattias [Uppsala University Hospital, Section of Medical Physics, Department of Oncology, Uppsala (Sweden)

    2012-04-15

    Radiolabelled Affibody molecules have demonstrated a potential for visualization of tumour-associated molecular targets. Affibody molecules (7 kDa) are composed of three alpha-helices. Recently, a smaller two-helix variant of Affibody molecules (5.1 kDa) was developed. The aim of this study was to compare two- and three-helix HER2-targeting Affibody molecules directly in vivo. The three-helix Affibody molecule ABY-002 and the two-helix Affibody molecule PEP09239 were labelled with {sup 111}In at the N-termini via DOTA chelator. Tumour-targeting properties were directly compared at 1 and 4 h after injection in mice bearing SKOV-3 xenografts with high HER2 expression and LS174T xenografts with low HER2 expression. The dissociation constants (K{sub D}) for HER2 binding were 78 pM for the three-helix Affibody molecule and 2.1 nM for the two-helix Affibody molecule. {sup 111}In-PEP09239 cleared more rapidly from the blood. In xenografts with high HER2 expression, the uptake of {sup 111}In-ABY-002 was significantly higher than that of {sup 111}In-PEP09239. The tumour-to-blood ratio was higher for {sup 111}In-PEP09239 at 4 h after injection, while there was no significant difference in other tumour-to-organ ratios. The tumour uptake of {sup 111}In-ABY-002 was eightfold higher than that of {sup 111}In-PEP09239 in xenografts with low expression. Tumour-to-blood ratios were equal in this case, but other tumour-to-organ ratios were appreciably higher for the three-helix variant. For tumours with high HER2 expression, two-helix HER2-targeting Affibody molecules can provide higher tumour-to-blood ratio at the cost of lower tumour uptake. In the case of low expression, both tumour uptake and tumour-to-organ ratios are appreciably higher for three-helix than for two-helix HER2-targeting Affibody molecules. (orig.)

  3. Radionuclide therapy of HER2-positive microxenografts using a 177Lu-labeled HER2-specific Affibody molecule.

    Science.gov (United States)

    Tolmachev, Vladimir; Orlova, Anna; Pehrson, Rikard; Galli, Joakim; Baastrup, Barbro; Andersson, Karl; Sandström, Mattias; Rosik, Daniel; Carlsson, Jörgen; Lundqvist, Hans; Wennborg, Anders; Nilsson, Fredrik Y

    2007-03-15

    A radiolabeled anti-HER2 Affibody molecule (Z(HER2:342)) targets HER2-expressing xenografts with high selectivity and gives good imaging contrast. However, the small size (approximately 7 kDa) results in rapid glomerular filtration and high renal accumulation of radiometals, thus excluding targeted therapy. Here, we report that reversible binding to albumin efficiently reduces the renal excretion and uptake, enabling radiometal-based nuclide therapy. The dimeric Affibody molecule (Z(HER2:342))(2) was fused with an albumin-binding domain (ABD) conjugated with the isothiocyanate derivative of CHX-A''-DTPA and labeled with the low-energy beta-emitter (177)Lu. The obtained conjugate [CHX-A''-DTPA-ABD-(Z(HER2:342))(2)] had a dissociation constant of 18 pmol/L to HER2 and 8.2 and 31 nmol/L for human and murine albumin, respectively. The radiolabeled conjugate displayed specific binding to HER2-expressing cells and good cellular retention in vitro. In vivo, fusion with ABD enabled a 25-fold reduction of renal uptake in comparison with the nonfused dimer molecule (Z(HER2:342))(2). Furthermore, the biodistribution showed high and specific uptake of the conjugate in HER2-expressing tumors. Treatment of SKOV-3 microxenografts (high HER2 expression) with 17 or 22 MBq (177)Lu-CHX-A''-DTPA-ABD-(Z(HER2:342))(2) completely prevented formation of tumors, in contrast to mice given PBS or 22 MBq of a radiolabeled non-HER2-binding Affibody molecule. In LS174T xenografts (low HER2 expression), this treatment resulted in a small but significant increase of the survival time. Thus, fusion with ABD improved the in vivo biodistribution, and the results highlight (177)Lu-CHX-A''-DTPA-ABD-(Z(HER2:342))(2) as a candidate for treatment of disseminated tumors with a high level of HER2 expression. PMID:17363599

  4. Influence of macrocyclic chelators on the targeting properties of (68Ga-labeled synthetic affibody molecules: comparison with (111In-labeled counterparts.

    Directory of Open Access Journals (Sweden)

    Joanna Strand

    Full Text Available Affibody molecules are a class of small (7 kDa non-immunoglobulin scaffold-based affinity proteins, which have demonstrated substantial potential as probes for radionuclide molecular imaging. The use of positron emission tomography (PET would further increase the resolution and quantification accuracy of Affibody-based imaging. The rapid in vivo kinetics of Affibody molecules permit the use of the generator-produced radionuclide (68Ga (T1/2=67.6 min. Earlier studies have demonstrated that the chemical nature of chelators has a substantial influence on the biodistribution properties of Affibody molecules. To determine an optimal labeling approach, the macrocyclic chelators 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA, 1,4,7-triazacyclononane-N,N,N-triacetic acid (NOTA and 1-(1,3-carboxypropyl-1,4,7- triazacyclononane-4,7-diacetic acid (NODAGA were conjugated to the N-terminus of the synthetic Affibody molecule ZHER2:S1 targeting HER2. Affibody molecules were labeled with (68Ga, and their binding specificity and cellular processing were evaluated. The biodistribution of (68Ga-DOTA-ZHER2:S1, (68Ga-NOTA-ZHER2:S1 and (68Ga-NODAGA-ZHER2:S1, as well as that of their (111In-labeled counterparts, was evaluated in BALB/C nu/nu mice bearing HER2-expressing SKOV3 xenografts. The tumor uptake for (68Ga-DOTA-ZHER2:S1 (17.9 ± 0.7%IA/g was significantly higher than for both (68Ga-NODAGA-ZHER2:S1 (16.13 ± 0.67%IA/g and (68Ga-NOTA-ZHER2:S1 (13 ± 3%IA/g at 2 h after injection. (68Ga-NODAGA-ZHER2:S1 had the highest tumor-to-blood ratio (60 ± 10 in comparison with both (68Ga-DOTA-ZHER2:S1 (28 ± 4 and (68Ga-NOTA-ZHER2:S1 (42 ± 11. The tumor-to-liver ratio was also higher for (68Ga-NODAGA-ZHER2:S1 (7 ± 2 than the DOTA and NOTA conjugates (5.5 ± 0.6 vs.3.3 ± 0.6. The influence of chelator on the biodistribution and targeting properties was less pronounced for (68Ga than for (111In. The results of this study demonstrate that macrocyclic

  5. PET imaging of insulin-like growth factor type 1 receptor expression with a 64Cu-labeled Affibody molecule.

    Science.gov (United States)

    Su, Xinhui; Cheng, Kai; Liu, Yang; Hu, Xiang; Meng, Shuxian; Cheng, Zhen

    2015-07-01

    The insulin-like growth factor 1 receptor (IGF-1R) serves as an attractive target for cancer molecular imaging and therapy. Previous single photon emission computerized tomography (SPECT) studies showed that the IGF-1R-targeting Affibody molecules (99m)Tc-ZIGF1R:4551-GGGC, [(99m)Tc(CO)3](+)-(HE)3-ZIGF1R:4551 and (111)In-DOTA-ZIGF1R:4551 can discriminate between high and low IGF-1R-expression tumors and have the potential for patient selection for IGF-1R-targeted therapy. Compared with SPECT, positron emission tomography (PET) may improve imaging of IGF-1R-expression, because of its high sensitivity, high spatial resolution, strong quantification ability. The aim of the present study was to develop the (64)Cu-labeled NOTA-conjugated Affibody molecule ZIGF-1R:4:40 as a PET probe for imaging of IGF-1R-positive tumor. An Affibody analogue (Ac-Cys-ZIGF-1R:4:40) binding to IGF-1R was site-specifically conjugated with NOTA and labeled with (64)Cu. Binding affinity and specificity of (64)Cu-NOTA-ZIGF-1R:4:40 to IGF-1R were evaluated using human glioblastoma U87MG cells. Small-animal PET, biodistribution, and metabolic stability studies were conducted on mice bearing U87MG xenografts after the injection of (64)Cu-NOTA-ZIGF-1R:4:40 with or without co-injection of unlabeled Affibody proteins. The radiosynthesis of (64)Cu-NOTA-ZIGF-1R:4:40 was completed successfully within 60 min with a decay-corrected yield of 75 %. (64)Cu-NOTA-ZIGF-1R:4:40 bound to IGF-1R with low nanomolar affinity (K D = 28.55 ± 3.95 nM) in U87MG cells. (64)Cu-NOTA-ZIGF-1R:4:40 also displayed excellent in vitro and in vivo stability. In vivo biodistribution and PET studies demonstrated targeting of U87MG gliomas xenografts was IGF-1R specific. The tumor uptake was 5.08 ± 1.07 %ID/g, and the tumor to muscle ratio was 11.89 ± 2.16 at 24 h after injection. Small animal PET imaging studies revealed that (64)Cu-NOTA-ZIGF-1R:4:40 could clearly identify U87MG tumors with good contrast at 1-24

  6. Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with 111In using a maleimido derivative of NODAGA

    International Nuclear Information System (INIS)

    Introduction: Affibody molecules have demonstrated potential for radionuclide molecular imaging. The aim of this study was to synthesize and evaluate a maleimido derivative of the 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid (NODAGA) for site-specific labeling of anti-HER2 Affibody molecule. Methods: The maleimidoethylmonoamide NODAGA (MMA-NODAGA) was synthesized and conjugated to ZHER2:2395 Affibody molecule having a C-terminal cysteine. Labeling efficiency, binding specificity to and cell internalization by HER2-expressing cells of [111In-MMA-NODAGA-Cys61]-ZHER2:2395 were studied. Biodistribution of [111In-MMA-NODAGA-Cys61]-ZHER2:2395 and [111In-MMA-DOTA-Cys61]-ZHER2:2395 was compared in mice. Results: The affinity of [MMA-NODAGA-Cys61]-ZHER2:2395 binding to HER2 was 67 pM. The 111In-labeling yield was 99.6%±0.5% after 30 min at 60°C. [111In-MMA-NODAGA-Cys61]-ZHER2:2395 bound specifically to HER2-expressing cells in vitro and in vivo. Tumor uptake of [111In-MMA-NODAGA-Cys61]-ZHER2:2395 in mice bearing DU-145 xenografts (4.7%±0.8% ID/g) was lower than uptake of [111In-MMA-DOTA-Cys61]-ZHER2:2395 (7.5%±1.6% ID/g). However, tumor-to-organ ratios were higher for [111In-MMA-NODAGA-Cys61]-ZHER2:2395 due to higher clearance rate from normal tissues. Conclusions: MMA-NODAGA is a promising chelator for site-specific labeling of targeting proteins containing unpaired cysteine. Appreciable influence of chelators on targeting properties of Affibody molecules was demonstrated.

  7. A HER2-binding Affibody molecule labelled with {sup 68}Ga for PET imaging: direct in vivo comparison with the {sup 111}In-labelled analogue

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    Tolmachev, Vladimir [Uppsala University, Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Uppsala University, Division of Nuclear Medicine, Department of Medical Sciences, Uppsala (Sweden); Velikyan, Irina [Uppsala University, Department of Biochemistry and Organic Chemistry, Uppsala (Sweden); GEMS PET Systems, GE Healthcare, Uppsala Applied Science Lab, Uppsala (Sweden); Sandstroem, Mattias [Uppsala University Hospital, Hospital Physics, Department of Oncology, Uppsala (Sweden); Orlova, Anna [Uppsala University, Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden)

    2010-07-15

    Overexpression of HER2 receptors is a prognostic and predictive biomarker in breast cancer and a number of other malignancies. Radionuclide molecular imaging of HER2 overexpression may influence patient management making treatment more personalized. Earlier, {sup 111}In-DOTA-Z{sub HER2:342-pep2} (ABY-002) Affibody molecule demonstrated excellent imaging of HER2-expressing xenografts in mice shortly after injection. The use of the positron-emitting nuclide {sup 68}Ga instead of {sup 111}In might increase both the sensitivity of HER2 imaging and accuracy of expression quantification. The goal of this study was to prepare and characterize {sup 68}Ga-labelled ABY-002. {sup 68}Ga labelling of ABY-002 was optimized. In vitro cell binding and procession of {sup 68}Ga-ABY-002 was evaluated. Biodistribution and tumour targeting of {sup 68}Ga-ABY-002 and {sup 111}In-ABY-002 was compared in vivo by paired-label experiments. ABY-002 was incubated with {sup 68}Ga at 90 C for 10 min resulting in a radiochemical labelling yield of over 95%. Capacity for specific binding to HER2-expressing cells was retained. In vivo, both {sup 68}Ga-ABY-002 and {sup 111}In-ABY-002 demonstrated specific targeting of SKOV-3 xenografts and high-contrast imaging. Background radioactivity in blood, lungs, gastrointestinal tract and muscle fell more rapidly for {sup 68}Ga-ABY-002 compared with {sup 111}In-ABY-002 favouring imaging shortly after injection. For {sup 68}Ga-ABY-002, a tumour uptake of 12.4 {+-} 3.8%ID/g and a tumour to blood ratio of 31 {+-} 13 were achieved at 2 h post-injection. {sup 68}Ga-ABY-002 is easy to label and provides high-contrast imaging within 2 h after injection. This makes it a promising candidate for clinical molecular imaging of HER2 expression in malignant tumours. (orig.)

  8. Influence of an aliphatic linker between DOTA and synthetic ZHER2:342 Affibody molecule on targeting properties of the 111In-labeled conjugate

    International Nuclear Information System (INIS)

    Introduction: Affibody molecules are small (∼6.5 kDa) scaffold proteins suitable for radionuclide imaging of tumor-associated molecular targets. Site-specific labeling of Affibody molecules made by peptide synthesis can be achieved by coupling a chelator to N-terminus in the last synthesis step. The goal of this study was to evaluate the influence of a 6-aminohexanoic linker between DOTA and ZHER2:342 on targeting properties of 111In-labeled conjugate. Methods: A DOTA-conjugated 6-aminohexanoic linker-containing variant of ZHER2:342 (ABY-003) was produced by peptide synthesis, and the in vitro binding affinity, specificity and cellular processing were evaluated. The biodistribution of 111In-ABY-003 in normal mice was compared to 111In-ABY-002 (DOTA-ZHER2:342-pep2) lacking the linker. Tumor-targeting properties of 111In-ABY-003 were evaluated in mice bearing HER2-expressing xenografts. Results: The dissociation constant of ABY-003 was in the low picomolar range, slightly higher than for ABY-002. 111In-ABY-003 bound specifically to HER2-expressing cells in vitro. The cellular retention was efficient but slightly worse than for 111In-ABY-002. In normal mice, the clearance of 111In-ABY-003 from blood and other tissues was slightly but significantly faster compared to 111In-ABY-002. Targeting of HER2-expressing xenografts by 111In-ABY-003 was receptor-specific. Due to faster clearance, the tumor-to-blood ratio for 111In-ABY-003 at 4 h postinjection was improved compared to 111In-ABY-002. The capacity of 111In-ABY-003 to visualize HER2-expressing tumors was confirmed by gamma camera imaging. Conclusions: A 6-aminohexanoic linker between the DOTA chelator and N-terminus of synthetic ZHER2:342 had a measurable effect on affinity, cellular retention of radioactivity and blood clearance. The linker might be used for modulation of targeting properties of Affibody molecules.

  9. Imaging of EGFR expression in murine xenografts using site-specifically labelled anti-EGFR 111In-DOTA-ZEGFR:2377 Affibody molecule: aspect of the injected tracer amount

    International Nuclear Information System (INIS)

    Overexpression of epidermal growth factor receptor (EGFR) is a prognostic and predictive biomarker in a number of malignant tumours. Radionuclide molecular imaging of EGFR expression in cancer could influence patient management. However, EGFR expression in normal tissues might complicate in vivo imaging. The aim of this study was to evaluate if optimization of the injected protein dose might improve imaging of EGFR expression in tumours using a novel EGFR-targeting protein, the DOTA-ZEGFR:2377 Affibody molecule. An anti-EGFR Affibody molecule, ZEGFR:2377, was labelled with 111In via the DOTA chelator site-specifically conjugated to a C-terminal cysteine. The affinity of DOTA-ZEGFR:2377 for murine and human EGFR was measured by surface plasmon resonance. The cellular processing of 111In-DOTA-ZEGFR:2377 was evaluated in vitro. The biodistribution of radiolabelled Affibody molecules injected in a broad range of injected Affibody protein doses was evaluated in mice bearing EGFR-expressing A431 xenografts. Site-specific coupling of DOTA provided a uniform conjugate possessing equal affinity for human and murine EGFR. The internalization of 111In-DOTA-ZEGFR:2377 by A431 cells was slow. In vivo, the conjugate accumulated specifically in xenografts and in EGFR-expressing tissues. The curve representing the dependence of tumour uptake on the injected Affibody protein dose was bell-shaped. The highest specific radioactivity (lowest injected protein dose) provided a suboptimal tumour-to-blood ratio. The results of the biodistribution study were confirmed by γ-camera imaging. The 111In-DOTA-ZEGFR:2377 Affibody molecule is a promising tracer for radionuclide molecular imaging of EGFR expression in malignant tumours. Careful optimization of protein dose is required for high-contrast imaging of EGFR expression in vivo. (orig.)

  10. In Vivo Imaging of Xenograft Tumors Using an Epidermal Growth Factor Receptor-Specific Affibody Molecule Labeled with a Near-infrared Fluorophore

    Directory of Open Access Journals (Sweden)

    Haibiao Gong

    2010-02-01

    Full Text Available Overexpression of epidermal growth factor receptor (EGFR is associated with many types of cancers. It is of great interest to noninvasively image the EGFR expression in vivo. In this study, we labeled an EGFR-specific Affibody molecule (Eaff with a near-infrared (NIR dye IRDye800CW maleimide and tested the binding of this labeled molecule (Eaff800 in cell culture and xenograft mouse tumor models. Unlike EGF, Eaff did not activate the EGFR signaling pathway. Results showed that Eaff800 was bound and taken up specifically by EGFR-overexpressing A431 cells. When Eaff800 was intravenously injected into nude mice bearing A431 xenograft tumors, the tumor could be identified 1 hour after injection and it became most prominent after 1 day. Images of dissected tissue sections demonstrated that the accumulation of Eaff800 was highest in the liver, followed by the tumor and kidney. Moreover, in combination with a human EGFR type 2 (HER2-specific probe Haff682, Eaff800 could be used to distinguish between EGFR- and HER2-overexpressing tumors. Interestingly, the organ distribution pattern and the clearance rate of Eaff800 were different from those of Haff682. In conclusion, Eaff molecule labeled with a NIR fluorophore is a promising molecular imaging agent for EGFR-overexpressing tumors.

  11. HER2-Positive Tumors Imaged Within 1 Hour Using a Site-Specifically 11C-Labeled Sel-Tagged Affibody Molecule

    OpenAIRE

    Wållberg, H; Grafström, J; Q. Cheng; Lu, L; Martinsson Ahlzén, HS; Samén, E; Thorell, JO; K. Johansson; Dunås, F; Olofsson, MH; Stone-Elander, S; Arnér, Elias S.J.; Ståhl, S

    2012-01-01

    A rapid, reliable method for distinguishing tumors or metastases that overexpress human epidermal growth factor receptor 2 (HER2) from those that do not is highly desired for individualizing therapy and predicting prognoses. In vivo imaging methods are available but not yet in clinical practice; new methodologies improving speed, sensitivity, and specificity are required. METHODS: A HER2-binding Affibody molecule, Z(HER2:342), was recombinantly fused with a C-terminal selenocystein...

  12. Cy5.5-labeled Affibody molecule for near-infrared fluorescent optical imaging of epidermal growth factor receptor positive tumors

    Science.gov (United States)

    Miao, Zheng; Ren, Gang; Liu, Hongguang; Jiang, Lei; Cheng, Zhen

    2010-05-01

    Affibody protein is an engineered protein scaffold with a three-helical bundle structure. Affibody molecules of small size (7 kD) have great potential for targeting overexpressed cancer biomarkers in vivo. To develop an Affibody-based molecular probe for in vivo optical imaging of epidermal growth factor receptor (EGFR) positive tumors, an anti-EGFR Affibody molecule, Ac-Cys-ZEGFR:1907 (7 kD), is site-specifically conjugated with a near-IR fluorescence dye, Cy5.5-mono-maleimide. Using fluorescent microscopy, the binding specificity of the probe Cy5.5-ZEGFR:1907 is checked by a high-EGFR-expressing A431 cell and low-EGFR-expressing MCF7 cells. The binding affinity of Cy5.5-ZEGFR:1907 (KD) to EGFR is 43.6+/-8.4 nM, as determined by flow cytometry. For an in vivo imaging study, the probe shows fast tumor targeting and good tumor contrast as early as 0.5 h postinjection (p.i.) for A431 tumors, while MCF7 tumors are barely visible. An ex vivo imaging study also demonstrates that Cy5.5-ZEGFR:1907 has high tumor, liver, and kidney uptakes at 24 h p.i.. In conclusion, Cy5.5-ZEGFR:1907 shows good affinity and high specificity to the EGFR. There is rapid achievement of good tumor-to-normal-tissue contrasts of Cy5.5-ZEGFR:1907, thus demonstrating its potential for EGFR-targeted molecular imaging of cancers.

  13. Influence of an aliphatic linker between DOTA and synthetic Z{sub HER2:342} Affibody molecule on targeting properties of the {sup 111}In-labeled conjugate

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    Tolmachev, Vladimir, E-mail: vladimir.tolmachev@bms.uu.se [Division of Biomedical Radiation Sciences, Department of Radiology, Oncology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala (Sweden); Feldwisch, Joachim [Division of Biomedical Radiation Sciences, Department of Radiology, Oncology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala (Sweden); Affibody AB, SE-112 51, Stockholm (Sweden); Lindborg, Malin; Baastrup, Barbro [Affibody AB, SE-112 51, Stockholm (Sweden); Sandstroem, Mattias [Hospital Physics, Department of Oncology, Uppsala University Hospital, Uppsala (Sweden); Orlova, Anna [Division of Biomedical Radiation Sciences, Department of Radiology, Oncology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala (Sweden)

    2011-07-15

    Introduction: Affibody molecules are small ({approx}6.5 kDa) scaffold proteins suitable for radionuclide imaging of tumor-associated molecular targets. Site-specific labeling of Affibody molecules made by peptide synthesis can be achieved by coupling a chelator to N-terminus in the last synthesis step. The goal of this study was to evaluate the influence of a 6-aminohexanoic linker between DOTA and Z{sub HER2:342} on targeting properties of {sup 111}In-labeled conjugate. Methods: A DOTA-conjugated 6-aminohexanoic linker-containing variant of Z{sub HER2:342} (ABY-003) was produced by peptide synthesis, and the in vitro binding affinity, specificity and cellular processing were evaluated. The biodistribution of {sup 111}In-ABY-003 in normal mice was compared to {sup 111}In-ABY-002 (DOTA-Z{sub HER2:342-pep2}) lacking the linker. Tumor-targeting properties of {sup 111}In-ABY-003 were evaluated in mice bearing HER2-expressing xenografts. Results: The dissociation constant of ABY-003 was in the low picomolar range, slightly higher than for ABY-002. {sup 111}In-ABY-003 bound specifically to HER2-expressing cells in vitro. The cellular retention was efficient but slightly worse than for {sup 111}In-ABY-002. In normal mice, the clearance of {sup 111}In-ABY-003 from blood and other tissues was slightly but significantly faster compared to {sup 111}In-ABY-002. Targeting of HER2-expressing xenografts by {sup 111}In-ABY-003 was receptor-specific. Due to faster clearance, the tumor-to-blood ratio for {sup 111}In-ABY-003 at 4 h postinjection was improved compared to {sup 111}In-ABY-002. The capacity of {sup 111}In-ABY-003 to visualize HER2-expressing tumors was confirmed by gamma camera imaging. Conclusions: A 6-aminohexanoic linker between the DOTA chelator and N-terminus of synthetic Z{sub HER2:342} had a measurable effect on affinity, cellular retention of radioactivity and blood clearance. The linker might be used for modulation of targeting properties of Affibody molecules.

  14. Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with 111In using N-terminal DOTA, NOTA and NODAGA chelators in mice bearing prostate cancer xenografts

    International Nuclear Information System (INIS)

    In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer. A synthetic variant of the anti-HER2 ZHER2:342 Affibody molecule, ZHER2:S1, was N-terminally conjugated with the chelators DOTA, NOTA and NODAGA. The conjugated proteins were biophysically characterized by electrospray ionization mass spectroscopy (ESI-MS), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR)-based biosensor analysis. After labelling with 111In, the biodistribution was assessed in normal mice and the two most promising conjugates were further evaluated for tumour targeting in mice bearing DU-145 prostate cancer xenografts. The HER2-binding equilibrium dissociation constants were 130, 140 and 90 pM for DOTA-ZHER2:S1, NOTA-ZHER2:S1 and NODAGA-ZHER2:S1, respectively. A comparative study of 111In-labelled DOTA-ZHER2:S1, NOTA-ZHER2:S1 and NODAGA-ZHER2:S1 in normal mice demonstrated a substantial influence of the chelators on the biodistribution properties of the conjugates. 111In-NODAGA-ZHER2:S1 had the most rapid clearance from blood and healthy tissues. 111In-NOTA-ZHER2:S1 showed high hepatic uptake and was excluded from further evaluation. 111In-DOTA-ZHER2:S1 and 111In-NODAGA-ZHER2:S1 demonstrated specific uptake in DU-145 prostate cancer xenografts in nude mice. The tumour uptake of 111In-NODAGA-ZHER2:S1, 5.6 ± 0.4%ID/g, was significantly lower than the uptake of 111In-DOTA-ZHER2:S1, 7.4 ± 0.5%ID/g, presumably because of lower bioavailability due to more rapid clearance. 111In-NODAGA-ZHER2:S1 provided higher tumour

  15. Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with {sup 111}In using N-terminal DOTA, NOTA and NODAGA chelators in mice bearing prostate cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Malmberg, Jennie; Varasteh, Zohreh; Orlova, Anna [Uppsala University, Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala (Sweden); Perols, Anna; Braun, Alexis; Eriksson Karlstroem, Amelie [AlbaNova University Centre, Division of Molecular Biotechnology, School of Biotechnology, KTH Royal Institute of Technology, Stockholm (Sweden); Altai, Mohamed; Tolmachev, Vladimir [Uppsala University, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Sandstroem, Mattias [Uppsala University Hospital, Section of Medical Physics, Department of Oncology, Uppsala (Sweden); Garske, Ulrike [Uppsala University Hospital, Department of Medical Sciences, Section of Nuclear Medicine, Uppsala (Sweden)

    2012-03-15

    In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer. A synthetic variant of the anti-HER2 Z{sub HER2:342} Affibody molecule, Z{sub HER2:S1}, was N-terminally conjugated with the chelators DOTA, NOTA and NODAGA. The conjugated proteins were biophysically characterized by electrospray ionization mass spectroscopy (ESI-MS), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR)-based biosensor analysis. After labelling with {sup 111}In, the biodistribution was assessed in normal mice and the two most promising conjugates were further evaluated for tumour targeting in mice bearing DU-145 prostate cancer xenografts. The HER2-binding equilibrium dissociation constants were 130, 140 and 90 pM for DOTA-Z{sub HER2:S1}, NOTA-Z{sub HER2:S1} and NODAGA-Z{sub HER2:S1}, respectively. A comparative study of {sup 111}In-labelled DOTA-Z{sub HER2:S1}, NOTA-Z{sub HER2:S1} and NODAGA-Z{sub HER2:S1} in normal mice demonstrated a substantial influence of the chelators on the biodistribution properties of the conjugates. {sup 111}In-NODAGA-Z{sub HER2:S1} had the most rapid clearance from blood and healthy tissues. {sup 111}In-NOTA-Z{sub HER2:S1} showed high hepatic uptake and was excluded from further evaluation. {sup 111}In-DOTA-Z{sub HER2:S1} and {sup 111}In-NODAGA-Z{sub HER2:S1} demonstrated specific uptake in DU-145 prostate cancer xenografts in nude mice. The tumour uptake of {sup 111}In-NODAGA-Z{sub HER2:S1}, 5.6 {+-} 0.4%ID/g, was significantly lower than the uptake of {sup 111}In-DOTA-Z{sub HER2:S1

  16. {sup 68}Ga-DOTA-affibody molecule for in vivo assessment of HER2/neu expression with PET

    Energy Technology Data Exchange (ETDEWEB)

    Kramer-Marek, Gabriela; Capala, Jacek [National Institutes of Health, National Cancer Institute, Bethesda, MD (United States); Shenoy, Nalini; Griffiths, Gary L. [National Institutes of Health, Imaging Probe Development Center, National Heart, Lung, and Blood Institute, Rockville, MD (United States); Seidel, Jurgen; Choyke, Peter [National Institutes of Health, Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD (United States)

    2011-11-15

    Overexpression of HER2/neu in breast cancer is correlated with a poor prognosis. It may vary between primary tumors and metastatic lesions and change during the treatment. Therefore, there is a need for a new means to assess HER2/neu expression in vivo. In this work, we used {sup 68}Ga-labeled DOTA-Z{sub HER2:2891}-Affibody to monitor HER2/neu expression in a panel of breast cancer xenografts. DOTA-Z{sub HER2:2891}-Affibody molecules were labeled with {sup 68}Ga. In vitro binding was characterized by a receptor saturation assay. Biodistribution and PET imaging studies were conducted in athymic nude mice bearing subcutaneous human breast cancer tumors with three different levels of HER2/neu expression. Nonspecific uptake was analyzed using non-HER2-specific Affibody molecules. Signal detected by PET was compared with ex vivo assessment of the tracer uptake and HER2/neu expression. The {sup 68}Ga-DOTA-Z{sub HER2:2891}-Affibody probe showed high binding affinity to MDA-MB-361 cells (K{sub D} = 1.4 {+-} 0.19 nM). In vivo biodistribution and PET imaging studies demonstrated high radioactivity uptake in HER2/neu-positive tumors. Tracer was eliminated quickly from the blood and normal tissues, resulting in high tumor-to-blood ratios. The highest concentration of radioactivity in normal tissue was seen in the kidneys (227 {+-} 14%ID/g). High-contrast PET images of HER2/neu-overexpressing tumors were recorded as soon as 1 h after tracer injection. A good correlation was observed between PET imaging, biodistribution estimates of tumor tracer concentration, and the receptor expression. These results suggest that PET imaging using {sup 68}Ga-DOTA-Z{sub HER2:2891}-Affibody is sensitive enough to detect different levels of HER2/neu expression in vivo. (orig.)

  17. Evaluation of backbone-cyclized HER2-binding 2-helix Affibody molecule for In Vivo molecular imaging

    OpenAIRE

    HONARVAR, HADIS; Jokilaakso, Nima; Andersson, Karl; Malmberg, Jennie; Rosik, Daniel; Orlova, Anna; Karlstrom, Amelie Eriksson; Tolmachev, Vladimir; Jarver, Peter

    2013-01-01

    Introduction Affibody molecules, small scaffold proteins, have demonstrated an appreciable potential as imaging probes. Affibody molecules are composed of three alpha-helices. Helices 1 and 2 are involved in molecular recognition, while helix 3 provides stability. The size of Affibody molecules can be reduced by omitting the third alpha-helix and cross-linking the two remaining, providing a smaller molecule with better extravasation and quicker clearance of unbound tracer. The goal of this st...

  18. Cellular studies of binding, internalization and retention of a radiolabeled EGFR-binding affibody molecule

    Energy Technology Data Exchange (ETDEWEB)

    Nordberg, Erika [Rudbeck Laboratory, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences, Uppsala University, SE-751 85 Uppsala (Sweden)], E-mail: erika.nordberg@bms.uu.se; Friedman, Mikaela [Department of Molecular Biotechnology, AlbaNova University Center, Kungl Tekniska Hoegskolan (KTH), SE-106 91 Stockholm (Sweden); Goestring, Lovisa [Rudbeck Laboratory, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences, Uppsala University, SE-751 85 Uppsala (Sweden); Affibody AB, PO Box 20137, SE-161 02 Bromma (Sweden); Adams, Gregory P. [Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111 (United States); Brismar, Hjalmar [Department of Cell Physics, AlbaNova University Center, Kungl Tekniska Hoegskolan (KTH), SE-106 91 Stockholm (Sweden); Nilsson, Fredrik Y. [Rudbeck Laboratory, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences, Uppsala University, SE-751 85 Uppsala (Sweden); Affibody AB, PO Box 20137, SE-161 02 Bromma (Sweden); Stahl, Stefan [Department of Molecular Biotechnology, AlbaNova University Center, Kungl Tekniska Hoegskolan (KTH), SE-106 91 Stockholm (Sweden); Glimelius, Bengt [Rudbeck Laboratory, Oncology, Radiology and Clinical Immunology, Uppsala University, SE-751 85 Uppsala (Sweden); Carlsson, Joergen [Rudbeck Laboratory, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences, Uppsala University, SE-751 85 Uppsala (Sweden)

    2007-08-15

    Introduction: The cellular binding and processing of an epidermal growth factor receptor (EGFR) targeting affibody molecule, (Z{sub EGFR:955}){sub 2}, was studied. This new and small molecule is aimed for applications in nuclear medicine. The natural ligand epidermal growth factor (EGF) and the antibody cetuximab were studied for comparison. Methods: All experiments were made with cultured A431 squamous carcinoma cells. Receptor specificity, binding time patterns, retention and preliminary receptor binding site localization studies were all made after {sup 125}I labeling. Internalization was studied using Oregon Green 488, Alexa Fluor 488 and CypHer5E markers. Results: [{sup 125}I](Z{sub EGFR:955}){sub 2} and [{sup 125}I]cetuximab gave a maximum cellular uptake of {sup 125}I within 4 to 8 h of incubation, while [{sup 125}I]EGF gave a maximum uptake already after 2 h. The retention studies showed that the cell-associated fraction of {sup 125}I after 48 h of incubation was {approx}20% when delivered as [{sup 125}I](Z{sub EGFR:955}){sub 2} and {approx}25% when delivered as [{sup 125}I]cetuximab. [{sup 125}I]EGF-mediated delivery gave a faster {sup 125}I release, where almost all cell-associated radioactivity had disappeared within 24 h. All three substances were internalized as demonstrated with confocal microscopy. Competitive binding studies showed that both EGF and cetuximab inhibited binding of (Z{sub EGFR:955}){sub 2} and indicated that the three substances competed for an overlapping binding site. Conclusion: The results gave information on cellular processing of radionuclides when delivered with (Z{sub EGFR:955}){sub 2} in comparison to delivery with EGF and cetuximab. Competition assays suggested that [{sup 125}I](Z{sub EGFR:955}){sub 2} bind to Domain III of EGFR. The affibody molecule (Z{sub EGFR:955}){sub 2} can be a candidate for EGFR imaging applications in nuclear medicine.

  19. Increasing the Net Negative Charge by Replacement of DOTA Chelator with DOTAGA Improves the Biodistribution of Radiolabeled Second-Generation Synthetic Affibody Molecules.

    Science.gov (United States)

    Westerlund, Kristina; Honarvar, Hadis; Norrström, Emily; Strand, Joanna; Mitran, Bogdan; Orlova, Anna; Eriksson Karlström, Amelie; Tolmachev, Vladimir

    2016-05-01

    A promising strategy to enable patient stratification for targeted therapies is to monitor the target expression in a tumor by radionuclide molecular imaging. Affibody molecules (7 kDa) are nonimmunoglobulin scaffold proteins with a 25-fold smaller size than intact antibodies. They have shown an apparent potential as molecular imaging probes both in preclinical and clinical studies. Earlier, we found that hepatic uptake can be reduced by the incorporation of negatively charged purification tags at the N-terminus of Affibody molecules. We hypothesized that liver uptake might similarly be reduced by positioning the chelator at the N-terminus, where the chelator-radionuclide complex will provide negative charges. To test this hypothesis, a second generation synthetic anti-HER2 ZHER2:2891 Affibody molecule was synthesized and labeled with (111)In and (68)Ga using DOTAGA and DOTA chelators. The chelators were manually coupled to the N-terminus of ZHER2:2891 forming an amide bond. Labeling DOTAGA-ZHER2:2891 and DOTA-ZHER2:2891 with (68)Ga and (111)In resulted in stable radioconjugates. The tumor-targeting and biodistribution properties of the (111)In- and (68)Ga-labeled conjugates were compared in SKOV-3 tumor-bearing nude mice at 2 h postinjection. The HER2-specific binding of the radioconjugates was verified both in vitro and in vivo. Using the DOTAGA chelator gave significantly lower radioactivity in liver and blood for both radionuclides. The (111)In-labeled conjugates showed more rapid blood clearance than the (68)Ga-labeled conjugates. The most pronounced influence of the chelators was found when they were labeled with (68)Ga. The DOTAGA chelator gave significantly higher tumor-to-blood (61 ± 6 vs 23 ± 5, p DOTA chelator. This study demonstrated that chelators may be used to alter the uptake of Affibody molecules, and most likely other scaffold-based imaging probes, for improvement of imaging contrast. PMID:27010700

  20. Site-specific labeling of affinity molecules for in vitro and in vivo studies

    OpenAIRE

    Perols, Anna

    2014-01-01

    The thesis is focused on site-specific labeling of affinity molecules for different applications where two types of binding proteins, Affibody molecules and antibodies, have been used. For the purpose of improving the properties of Affibody molecules for in vivo imaging, novel bi-functional chelators for radiolabeling using the radionuclide 111In were evaluated. In a first study, two chelators denoted NOTA and DOTA, respectively, were separately conjugated via maleimide chemistry to a C-termi...

  1. Imaging of HER3-expressing xenografts in mice using a {sup 99m}Tc(CO){sub 3}-HEHEHE-Z{sub HER3:08699} affibody molecule

    Energy Technology Data Exchange (ETDEWEB)

    Orlova, Anna; Rosestedt, Maria; Varasteh, Zohreh; Selvaraju, Ram Kumar [Uppsala University, Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala (Sweden); Malm, Magdalena; Andersson, Ken; Staahl, Stefan; Loefblom, John [KTH Royal Institute of Technology, Division of Protein Technology, School of Biotechnology, Stockholm (Sweden); Altai, Mohamed; Honarvar, Hadis; Strand, Joanna; Tolmachev, Vladimir [Uppsala University, Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden)

    2014-07-15

    Human epidermal growth factor receptor type 3 (HER3) is a transmembrane receptor tyrosine kinase belonging to the HER (ErbB) receptor family. Membranous expression of HER3 is associated with trastuzumab resistance in breast cancer and the transition to androgen independence in prostate cancer. Imaging of HER3 expression in malignant tumors may provide important diagnostic information that can influence patient management. Affibody molecules with low picomolar affinity to HER3 were recently selected. The aim of this study was to investigate the feasibility of HER3 imaging using radiolabeled Affibody molecules. A HER3-binding Affibody molecule, Z{sub 08699}, with a HEHEHE-tag on N-terminus was labeled with {sup 99m}Tc(CO){sub 3} using an IsoLink kit. In vitro and in vivo binding specificity and the cellular processing of the labeled binder were evaluated. Biodistribution of {sup 99m}Tc(CO){sub 3}-HEHEHE-Z{sub 08699} was studied over time in mice bearing HER3-expressing xenografts. HEHEHE-Z{sub 08699} was labeled with {sup 99m}Tc(CO){sub 3} with an isolated yield of >80 % and a purity of >99 %. Binding of {sup 99m}Tc(CO){sub 3}-HEHEHE-Z{sub 08699} was specific to BT474 and MCF7 (breast cancer), and LS174T (colon cancer) cells. Cellular processing showed rapid binding and relatively quick internalization of the receptor/Affibody molecule complex (70 % of cell-associated radioactivity was internalized after 24 h). The tumor targeting was receptor mediated and the excretion was predominantly renal. Receptor-mediated uptake was also found in the liver, lung, stomach, intestine, and salivary glands. At 4 h pi, tumor-to-blood ratios were 7 ± 3 for BT474, and 6 ± 2 for LS174T xenografts. LS174T tumors were visualized by microSPECT 4 h pi. The results of this study suggest the feasibility of HER3-imaging in malignant tumors using Affibody molecules. (orig.)

  2. The influence of Bz-DOTA and CHX-A''-DTPA on the biodistribution of ABD-fused anti-HER2 Affibody molecules: implications for 114mIn-mediated targeting therapy

    International Nuclear Information System (INIS)

    Affibody molecules represent a novel class of high-affinity agents for radionuclide tumour targeting. Fusion of the Affibody molecules with an albumin-binding domain (ABD) enables modification of the blood kinetics of the Affibody molecules and reduction of the renal dose. 177Lu-CHX-A''-DTPA-ABD-(ZHER2:342)2, an anti-HER2 Affibody molecule-ABD fusion protein has earlier demonstrated promising results in treatment of HER2-expressing micro-xenografts in mice. The use of the in vivo generator 114mIn/114In as a label for ABD-fused Affibody molecules would create preconditions for efficient treatment of both micrometastases (due to conversion and Auger electrons of 114mIn) and bulky tumours (due to high-energy beta particles from the daughter nuclide 114In). The goal of this study was to investigate if different chelators influence the biodistribution of ABD-(ZHER2:342)2 and to find an optimal chelator for attachment of 114mIn to the Affibody molecule-ABD fusion protein. Isothiocyanate derivatives of Bz-DOTA and CHX-A''-DTPA were coupled to ABD-(ZHER2:342)2. The cellular processing of both conjugates was studied in vitro. The influence of chelators on the biodistribution was investigated in mice using double isotope (114mIn and 111In) labelling. The apparent affinity of CHX-A''-DTPA-ABD-(ZHER2:342)2 and Bz-DOTA-ABD-(ZHER2:342)2 to the extracellular domain of HER2 was similar, 13.5 and 15.0 pM, respectively. It was found that both conjugates were internalized by SKOV-3 cells. The use of CHX-A''-DTPA provided better cellular retention of the radioactivity, better tumour accumulation of radioactivity and better tumour to organ dose ratios than Bz-DOTA-ABD-(ZHER2:342)2. CHX-A''-DTPA is more suitable for 114mIn labelling of Affibody molecule-ABD fusion proteins for radionuclide therapy. (orig.)

  3. Radiolabeled Affibody-Albumin Bioconjugates for HER2 Positive Cancer Targeting

    OpenAIRE

    Hoppmann, Susan; Miao, Zheng; Liu, Shuanglong; Liu, Hongguang; REN, GANG; Bao, Ande; Cheng, Zhen

    2011-01-01

    Affibody molecules have received significant attention in the fields of molecular imaging and drug development. However, Affibody scaffolds display an extremely high renal uptake, especially when modified with chelators and then labeled with radiometals. This unfavorable property may impact their use as radiotherapeutic agents in general and as imaging probes for the detection of tumors adjacent to kidneys in particular. Herein, we present a simple and generalizable strategy for reducing the ...

  4. In vivo targeting of HER2-positive tumor using 2-helix affibody molecules

    OpenAIRE

    Ren, Gang; Webster, Jack M.; LIU, ZHE; Zhang, Rong; Miao, Zheng; Liu, Hongguang; Gambhir, Sanjiv S.; Syud, Faisal A.; Cheng, Zhen

    2011-01-01

    Molecular imaging of human epidermal growth factor receptor type 2 (HER2) expression has drawn significant attention because of the unique role of the HER2 gene in diagnosis, therapy and prognosis of human breast cancer. In our previous research, a novel cyclic 2-helix small protein, MUT-DS, was discovered as an anti-HER2 Affibody analog with high affinity through rational protein design and engineering. MUT-DS was then evaluated for positron emission tomography (PET) of HER2-positive tumor b...

  5. 抗人表皮生长因子受体2亲和体 ZHER2瞷342的18F 标记及靶向胃癌的示踪研究%Tracing investigation of targeting gastric cancer with 18F labeled anti-human epidermal growth factor receptor 2 specific affibody molecule ZHER2:342

    Institute of Scientific and Technical Information of China (English)

    潘云云; 柏志成; 潘栋辉; 徐宇平; 杨润林; 王立振; 管文贤; 杨敏

    2016-01-01

    目的:探讨18 F标记抗人表皮生长因子受体2( HER2)亲和体探针在HER2过表达胃癌中的示踪作用。方法化学合成制备C末端含半胱氨酸的抗HER2亲和体 ZHER2瞷342,通过双功能螯合剂1,4,7-三氮杂环壬烷-1,4,7三乙酸的马来酰亚胺衍生物( NOTA-MAL)与巯基的加成反应合成NOTA-MAL-Cys59-ZHER2:342偶联物(简称偶联物),经18 FAl一步法定位标记制得新型HER2靶向分子探针18FAl-NOTA-MAL-Cys59ZHER2瞷342(简称探针),并经高效液相色谱法(HPLC)进行质量控制。构建NOD SCID鼠HER2高表达胃癌NCI N87移植瘤模型。进行体外细胞摄取、阻断、竞争结合实验和模型鼠micro PET显像以评价探针的靶向能力。结果18 F标记探针放化纯度>95%。细胞结合实验显示HER2过表达NCI N87细胞对18 F标记亲和体的摄取速度快,孵育15 min后接近摄取高峰,约(7.48±0.49)%ID。阻断HER2后,细胞对标记物的摄取水平显著下降,15 min 为(0.85±0.09)%ID (P<0.05),说明NCI N87对亲和体的摄取是通过HER2所特异性介导的。细胞竞争结合实验测得IC50为9.4 nM,说明探针与HER2结合亲和力高。 NOD SCID鼠micro PET显像肿瘤摄取高,30 min为(7.22±0.24)%ID/g。阻断组micro PET显像肿瘤摄取显著降低,1h为(2.56±0.11)%ID/g(P<0.05)。探针主要经肾脏排泄。结论新型探针标记方便,对HER2过表达胃癌靶向能力强。%Objective To investigate the effect of 18 F labeled anti-HER2 affibody probe on the targeting HER2 overexpressed human gastric cancer with micro PET imaging . Methods Anti-HER2 specific affibody ZHER2:342 was obtained from chemical synthesis routes .The bifunctional maleimide derivative of 1,4,7-Triazacyclononane-1,4,7-triacetic acid (NOTA) was coupled to thiol-group of cysteine of ZHER2:342 to form the chelator-peptide conjugation .Then the newly produced 18 F

  6. Imaging of platelet-derived growth factor receptor β expression in glioblastoma xenografts using affibody molecule 111In-DOTA-Z09591

    OpenAIRE

    TOLMACHEV, VLADIMIR; Varasteh, Zohreh; HONARVAR, HADIS; Hosseinimehr, Seyed Jalal; Eriksson, Olof; Jonasson, Per; Frejd, Fredrik Y.; Abrahmsen, Lars; ORLOVA, ANNA

    2014-01-01

    The overexpression and excessive signaling of platelet-derived growth factor receptor β (PDGFRβ) has been detected in cancers, atherosclerosis, and a variety of fibrotic diseases. Radionuclide in vivo visualization of PDGFRβ expression might help to select PDGFRβ targeting treatment for these diseases. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of PDGFRβ expression using an Affibody molecule, a small nonimmunoglobulin affinity protein. Methods The P...

  7. Labelled molecules, modern research implements

    International Nuclear Information System (INIS)

    Details of the synthesis of carbon 14- and tritium-labelled molecules are examined. Although the methods used are those of classical organic chemistry the preparation of carbon 14-labelled molecules differs in some respects, most noticeably in the use of 14CO2 which requires very special handling techniques. For the tritium labelling of organic molecules the methods are somewhat different, very often involving exchange reactions. The following are described in turn: the so-called Wilzbach exchange method; exchange by catalysis in solution; catalytic hydrogenation with tritium; reductions with borotritides. Some applications of labelled molecules in organic chemistry, biochemistry and pharmacology are listed

  8. EGFR-directed Affibody for fluorescence-guided glioma surgery: time-dose analysis (Conference Presentation)

    Science.gov (United States)

    Ribeiro de Souza, Ana Luiza; Marra, Kayla; Gunn, Jason R.; Elliott, Jonathan T.; Samkoe, Kimberley S.; Paulsen, Keith D.; Draney, Daniel R.; Feldwisch, Joachim

    2016-03-01

    The key to fluorescence guided surgical oncology is the ability to create specific contrast between normal and glioma tissue. The blood brain barrier that limits the delivery of substances to the normal brain is broken in tumors, allowing accumulation of agents in the tumor interior. However, for a clinical success, imaging agents should be in the infiltrative edges to minimize the resection of normal brain while enable the removal of tumor. The aberrant overexpression and/or activation of EGFR is associated with many types of cancers, including glioblastoma and the injection of a fluorescent molecule targeted to these receptors would improve tumor contrast during fluorescence guided surgery. Affibody molecules have intentional medium affinity and high potential specificity, which are the desirable features of a good surgical imaging agent. The aim of this study was evaluate the brain/glioma uptake of ABY029 labeled with near-infrared dye IRDye800CW after intravenous injection. Rats were either inoculated with orthotopic implantations of U251 human glioma cell line or PBS (shams control) in the brain. The tumors were allowed to grow for 2-3 weeks before carrying out fluorescent tracer experiments. Fluorescent imaging of ex vivo brain slices from rats was acquired at different time points after infection of fluorescently labeled EGFR-specific affibody to verify which time provided maximal contrast tumor to normal brain. Although the tumor was most clearly visualized after 1h of IRDye800CW-labeled ABY029 injection, the tumor location could be identified from the background after 48h. These results suggest that the NIR-labeled affibody examined shows excellent potential to increase surgical visualization for confirmed EGFR positive tumors.

  9. The tritium labelling of organic molecules by heterogeneous catalytic exchange

    International Nuclear Information System (INIS)

    The influence of the temperature at 65 degree centigree and 120 degree centigree on the labelling of three organic molecules with tritium was studied. The compounds were: benzoic acid, de phenyl glyoxal and 2,3-tetramethylene-4-pantothenyl-7-oxo diacetin.The method employed was the heterogeneous catalytic exchange between tritiated water and the organic compound. The purification was made by thin-layer chromatography and the concentration, purity and specific activity of the products were determined by counting and ultraviolet techniques. The thermal stability and the radiolytic effects on labelled benzoic acid were also considered. (Author) 9 refs

  10. Multinuclear NMR of 15 N labelled organic molecules

    International Nuclear Information System (INIS)

    The paper presents the application of multinuclear NMR techniques to the study of 15 N labeled organic molecules. There are some important points of great interest in such type of research, namely, structure determination, i.e. location of the 15 N in molecule and determination of 15 N concentration in order to obtain quantitative results about the intramolecular short and long range interaction. Different NMR techniques were used in the study of 13 C, 1 H and 15 N. Obtaining the 15 N NMR signal imposes some special preparation of the spectrometer. First, we had to manage a very large spectral window (-400 to +1200 ppm) which makes difficult finding the signal. Secondly, in the condition of proton decoupling, in a very large band, a decrease of the signal can occur due to the NOE negative effect. To avoid this effect, other decoupling method, called 'inverse gated 1 H decoupling' was used. As a reference, for 15 N, we used CH3NO2, fixed at 0 ppm. In order to find the suitable spectral window we used the formamide (15 N). The results of obtaining the 15 N-labeled procaine are presented. (author)

  11. Technetium-99m Labelled Molecules for Hypoxia Imaging. Chapter 15

    International Nuclear Information System (INIS)

    In the field of diagnostic imaging, the concept of imaging hypoxia constitutes an important development and 99mTc labelled vectors have taken a long stride in this direction. Delineation of hypoxic cells amidst oxygenated cells has a strong bearing on treatment strategies and regimes, since hypoxic cells are normally resistant to therapy, thus having a direct influence on the extent of tumour propagation and malignant progression. Inherent drawbacks in the invasive methods currently available for measuring hypoxia led to the development of non-invasive modalities such as use of radiolabelled molecules for imaging hypoxia. In the chapter, an attempt is made to provide a comprehensive overview of 99mTc based radiopharmaceutical agents as well as a brief discussion of other radiolabelled agents that show considerable promise in diagnostic imaging of tumour hypoxia. The review also discusses the phenomenon of hypoxia, other non-invasive methods of detecting hypoxia currently available and the evolution of radiopharmaceuticals to image hypoxia. (author)

  12. Selective Chemical Labeling of Proteins with Small Fluorescent Molecules Based on Metal-Chelation Methodology

    OpenAIRE

    Nobuaki Soh

    2008-01-01

    Site-specific chemical labeling utilizing small fluorescent molecules is a powerful and attractive technique for in vivo and in vitro analysis of cellular proteins, which can circumvent some problems in genetic encoding labeling by large fluorescent proteins. In particular, affinity labeling based on metal-chelation, advantageous due to the high selectivity/simplicity and the small tag-size, is promising, as well as enzymatic covalent labeling, thereby a variety of novel methods have been stu...

  13. Label-enhanced surface plasmon resonance applied to label-free interaction analysis of small molecules and fragments.

    Science.gov (United States)

    Eng, Lars; Nygren-Babol, Linnéa; Hanning, Anders

    2016-10-01

    Surface plasmon resonance (SPR) is a well-established method for studying interactions between small molecules and biomolecules. In particular, SPR is being increasingly applied within fragment-based drug discovery; however, within this application area, the limited sensitivity of SPR may constitute a problem. This problem can be circumvented by the use of label-enhanced SPR that shows a 100-fold higher sensitivity as compared with conventional SPR. Truly label-free interaction data for small molecules can be obtained by applying label-enhanced SPR in a surface competition assay format. The enhanced sensitivity is accompanied by an increased specificity and inertness toward disturbances (e.g., bulk refractive index disturbances). Label-enhanced SPR can be used for fragment screening in a competitive assay format; the competitive format has the added advantage of confirming the specificity of the molecular interaction. In addition, label-enhanced SPR extends the accessible kinetic regime of SPR to the analysis of very fast fragment binding kinetics. In this article, we demonstrate the working principles and benchmark the performance of label-enhanced SPR in a model system-the interaction between carbonic anhydrase II and a number of small-molecule sulfonamide-based inhibitors. PMID:27325502

  14. A study on rhenium labelling for several small molecule ligands

    International Nuclear Information System (INIS)

    Objective: Several chemical reactions were studied with the theory of complex chemistry for finding out the objective law of rhenium labelling. Methods: Some kinds of ligands were complexed to rhenium, and the effects were observed in different reactive conditions. The results were analysed with the theories of chemical thermodynamics, chemical dynamics and structure chemistry. Results: 188Re-glucoheptonate (GH): in the condition of pH 2, SnCl2 1 mg, 30 min at room temperature, the labelling ratio was 85.9%. 188Re-methylene-diphosphonate (MDP): in the condition of pH 2, SnCl2 1mg, 30 min at room temperature, the labelling ratio was 85%. 188Re-MIBI: in the condition of pH 2, SnCl2 1 mg, 30 min at 100 degree C, the labelling ratio was 58%. 188Re-citric acid: in the condition of pH 2, SnCl2 1 mg, 30 min at room temperature, the labelling ratio was 92.1%. Conclusion: The theory generated from chemical experiments can be used to direct rhenium labelling and develop the application of rhenium in basic research and clinical diagnosis and therapy

  15. Semiconductor Quantum Rods as Single Molecule FluorescentBiological Labels

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Aihua; Gu, Weiwei; Boussert, Benjamine; Koski, Kristie; Gerion, Daniele; Manna, Liberato; Le Gros, Mark; Larabell, Carolyn; Alivisatos, A. Paul

    2006-05-29

    In recent years, semiconductor quantum dots have beenapplied with great advantage in a wide range of biological imagingapplications. The continuing developments in the synthesis of nanoscalematerials and specifically in the area of colloidal semiconductornanocrystals have created an opportunity to generate a next generation ofbiological labels with complementary or in some cases enhanced propertiescompared to colloidal quantum dots. In this paper, we report thedevelopment of rod shaped semiconductor nanocrystals (quantum rods) asnew fluorescent biological labels. We have engineered biocompatiblequantum rods by surface silanization and have applied them fornon-specific cell tracking as well as specific cellular targeting. Theproperties of quantum rods as demonstrated here are enhanced sensitivityand greater resistance for degradation as compared to quantum dots.Quantum rods have many potential applications as biological labels insituations where their properties offer advantages over quantumdots.

  16. Influence of quantum dot labels on single molecule movement in the plasma membrane

    DEFF Research Database (Denmark)

    Clausen, Mathias P.; Lagerholm, B. Christoffer

    2011-01-01

    Single particle tracking results are very dependent on the probe that is used. In this study we have investigated the influence that functionalized quantum dots (QDs) have on the recorded movement in single molecule tracking experiments of plasma membrane species in live cells. Potential issues in...... simultaneous investigations of different plasma membrane species in order to discriminate the effect of the label from differences in movement of the target molecules....

  17. Conformational dynamics of nucleic acid molecules studied by PELDOR spectroscopy with rigid spin labels

    Science.gov (United States)

    Prisner, T. F.; Marko, A.; Sigurdsson, S. Th.

    2015-03-01

    Nucleic acid molecules can adopt a variety of structures and exhibit a large degree of conformational flexibility to fulfill their various functions in cells. Here we describe the use of Pulsed Electron-Electron Double Resonance (PELDOR or DEER) to investigate nucleic acid molecules where two cytosine analogs have been incorporated as spin probes. Because these new types of spin labels are rigid and incorporated into double stranded DNA and RNA molecules, there is no additional flexibility of the spin label itself present. Therefore the magnetic dipole-dipole interaction between both spin labels encodes for the distance as well as for the mutual orientation between the spin labels. All of this information can be extracted by multi-frequency/multi-field PELDOR experiments, which gives very precise and valuable information about the structure and conformational flexibility of the nucleic acid molecules. We describe in detail our procedure to obtain the conformational ensembles and show the accuracy and limitations with test examples and application to double-stranded DNA.

  18. Rapid localization of carbon 14-labeled molecules in biological samples by ion mass microscopy

    International Nuclear Information System (INIS)

    We report here on the ability of secondary ion mass spectrometry (SIMS) to provide rapid imaging of the intracellular distribution of 14C-labeled molecules. The validity of this method, using mass discrimination of carbon 14 atoms, was assessed by imaging the distribution of two molecules of well-known metabolism, [14C]-thymidine and [14C]-uridine, incorporated by human fibroblasts in culture. As expected, 14C ion images showed the presence of [14C]-thymidine in the nucleus of dividing cells, whereas [14C]-uridine was present in the cytoplasm as well as the nucleus of all cells, with a large concentration in the nucleoli. The time required to obtain the distribution images with the SMI 300 microscope was less than 6 min, whereas microautoradiography, the classical method for mapping the tissue distribution of 14C-labeled molecules, usually requires exposure times of several months. Secondary ion mass spectrometry using in situ mass discrimination is proposed here as a very sensitive method which permits rapid imaging of the subcellular distribution of molecules labeled with carbon 14

  19. Examples of the use of preparatory gas-chromatography in the manufacture of labelled molecules

    International Nuclear Information System (INIS)

    Gas chromatography is the most commonly used in the analysis of volatile products. Certain works mention its use for preparatory purposes. Since organic labelled-molecule preparations are usually made in respect of quantities of the order of 1-10 mmole, it has been possible to use gas chromatography with very little alteration for the purification of C14-labelled molecules and their separation from complex reaction mixtures. The apparatus employed is briefly described. The chromatography columns used (diam.: 9-12 mm, length: approx. 4-6 m) made it possible to separate labelled products with boiling-points of up to 180o C and in quantities of approximately 100 mg to 1 g. The fractions detected by a conventional conductivity-cell device were condensed in traps cooled by liquid nitrogen. The radioactivity was not measured at the same time, as an ionization chamber capable of operating at up to 200oC is still only at the research stage. In all cases, the vector gas was helium and the stationary phase support was usually 80 mesh ''celite 545''. Examples are given of applications to the purification of acetone 1-3-C14, benzene C414 methyl or ethyl acrylate 2-3-C14 and butadiene D6, and to the separation of a mixture of aromatic hydrocarbures. (author)

  20. Stable isotope labeling of glycoprotein expressed in silkworms using immunoglobulin G as a test molecule

    Energy Technology Data Exchange (ETDEWEB)

    Yagi, Hirokazu [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan); Nakamura, Masatoshi [National Institute of Agrobiological Sciences, Genetic Resources Conservation Research Unit, Genetic Resources Center (Japan); Yokoyama, Jun [Taiyo Nippon Sanso Corporation, Tsukuba Laboratories (Japan); Zhang, Ying; Yamaguchi, Takumi [National Institutes of Natural Sciences, Institute for Molecular Science and Okazaki Institute for Integrative Bioscience (Japan); Kondo, Sachiko [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan); Kobayashi, Jun [Yamaguchi University, Department of Biological and Environmental Sciences, Faculty of Agriculture (Japan); Kato, Tatsuya; Park, Enoch Y. [Shizuoka University, Laboratory of Biotechnology, Research Institute of Green Science and Technology (Japan); Nakazawa, Shiori [Nagoya University, Sugashima Marine Biological Laboratory, Graduate School of Science (Japan); Hashii, Noritaka; Kawasaki, Nana [National Institute of Health Sciences, Division of Biological Chemistry and Biologicals (Japan); Kato, Koichi, E-mail: kkato@phar.nagoya-cu.ac.jp [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan)

    2015-06-15

    Silkworms serve as promising bioreactors for the production of recombinant proteins, including glycoproteins and membrane proteins, for structural and functional protein analyses. However, lack of methodology for stable isotope labeling has been a major deterrent to using this expression system for nuclear magnetic resonance (NMR) structural biology. Here we developed a metabolic isotope labeling technique using commercially available silkworm larvae. The fifth instar larvae were infected with baculoviruses for co-expression of recombinant human immunoglobulin G (IgG) as a test molecule, with calnexin as a chaperone. They were subsequently reared on an artificial diet containing {sup 15}N-labeled yeast crude protein extract. We harvested 0.1 mg of IgG from larva with a {sup 15}N-enrichment ratio of approximately 80 %. This allowed us to compare NMR spectral data of the Fc fragment cleaved from the silkworm-produced IgG with those of an authentic Fc glycoprotein derived from mammalian cells. Therefore, we successfully demonstrated that our method enables production of isotopically labeled glycoproteins for NMR studies.

  1. Stable isotope labeling of glycoprotein expressed in silkworms using immunoglobulin G as a test molecule

    International Nuclear Information System (INIS)

    Silkworms serve as promising bioreactors for the production of recombinant proteins, including glycoproteins and membrane proteins, for structural and functional protein analyses. However, lack of methodology for stable isotope labeling has been a major deterrent to using this expression system for nuclear magnetic resonance (NMR) structural biology. Here we developed a metabolic isotope labeling technique using commercially available silkworm larvae. The fifth instar larvae were infected with baculoviruses for co-expression of recombinant human immunoglobulin G (IgG) as a test molecule, with calnexin as a chaperone. They were subsequently reared on an artificial diet containing 15N-labeled yeast crude protein extract. We harvested 0.1 mg of IgG from larva with a 15N-enrichment ratio of approximately 80 %. This allowed us to compare NMR spectral data of the Fc fragment cleaved from the silkworm-produced IgG with those of an authentic Fc glycoprotein derived from mammalian cells. Therefore, we successfully demonstrated that our method enables production of isotopically labeled glycoproteins for NMR studies

  2. Problems Associated with the Use of Labelled Molecules in Biology and Medicine. General Review

    International Nuclear Information System (INIS)

    A general review is given on problems associated with the use of labelled molecules in the life sciences. Three areas of interest were selected for discussion concerning: (a) the tracer molecule; (b) aspects of cellular metabolism; and (c) the toxicity of the incorporated isotopes. In respect of the tracer molecule, specificity of labelling (especially that with tritium), radiochemical purity, biological stability (particularly in the case of tritia ted precursors) and kinetic isotope effects are discussed. The paper also covers various aspects of cellular metabolism, such as the importance of cellular specificity of enzymes, the size of the ''soluble pool'', and control of pool equilibrium, as well as the implication of cell proliferation on isotope content, the relationship between cell cycle and radiosensitivity, factors influencing the duration of the cell cycle, problems of precursor availability and rate of cellular incorporation - including the contribution from precursor reutilization - and the importance of the geometry of the incorporated precursor. The discussion on the toxicity of incorporated isotopes gives an introduction to transmutation effects, aside from radiation effects and considers the transmutation effects of tritium, 14C, 35S and 32P. Attention is called to the possible biological implications of the Auger effect. (author)

  3. Fluorescent labeling of NASBA amplified tmRNA molecules for microarray applications

    Directory of Open Access Journals (Sweden)

    Kaplinski Lauris

    2009-05-01

    Full Text Available Abstract Background Here we present a novel promising microbial diagnostic method that combines the sensitivity of Nucleic Acid Sequence Based Amplification (NASBA with the high information content of microarray technology for the detection of bacterial tmRNA molecules. The NASBA protocol was modified to include aminoallyl-UTP (aaUTP molecules that were incorporated into nascent RNA during the NASBA reaction. Post-amplification labeling with fluorescent dye was carried out subsequently and tmRNA hybridization signal intensities were measured using microarray technology. Significant optimization of the labeled NASBA protocol was required to maintain the required sensitivity of the reactions. Results Two different aaUTP salts were evaluated and optimum final concentrations were identified for both. The final 2 mM concentration of aaUTP Li-salt in NASBA reaction resulted in highest microarray signals overall, being twice as high as the strongest signals with 1 mM aaUTP Na-salt. Conclusion We have successfully demonstrated efficient combination of NASBA amplification technology with microarray based hybridization detection. The method is applicative for many different areas of microbial diagnostics including environmental monitoring, bio threat detection, industrial process monitoring and clinical microbiology.

  4. A study on labelling of bioactive molecules using 99mTc(CO)3(H2O)3+ precursor

    International Nuclear Information System (INIS)

    To radiolable bioactive molecules, we synthesized 99mTc precursor, 99mTc(CO)3(H2O)3+ with a low oxidation state (1). We evaluated the characteristics of bioactive molecules labeled with precursor using in vitro and in vivo study. The 99mTc(CO)3(H2O)3+ was synthesized by low pressure carbonylation (1 atm CO) of 99mTcO)4- in the presence of NaBH4 with high labeling yield (>98%) and stability up to 8 hrs. A prepared 99mTc(CO)3(H2O)3+ was reacted with common ligands for 99mTc labeling and amino acids to investigate labeling property of 99mTc(CO)3(H2O)3+. And we also assessed the biodistribution property of 99mTc(CO)3(H2O)3+-complexes in rabbit. 99mTc-tricarbonyl complexes with ligands for 99mTc labeling was also easily prepared and the properties of biodistribution differ between 99mTc-tricarbonyl labeling group and 99mTc labeling one. From these results, we concluded that 99mTc(CO)3(H2O)3+ and 99mTc-tricarbonyl complex is a potential precursor for the development of radiopharmaceuticals, especially for labeling of biomolecules

  5. Synthesis and study of the biodistribution of a new molecule labeled by technetium 99M

    International Nuclear Information System (INIS)

    Cytectrenes are stable complexes, neutral, low-weight molecular and lipophilic, that's allowing them to be able to cross the intact BBB. These piperidinic molecules are synthesized by atomic exchange between tricarbonyl technetium with the Fe-Cyclopentadienyl fragment. The labelling reaction is carried out classically in oil bath at a temperature of 150 C during one hour. The reaction can be optimized using microwave. The study of the biodistribution in rat of these complexes after there purification shows high cerebral uptake. Cytectrenes can be used as a potential cerebral radiotracers for the early diagnosis of neuropsychiatric diseases. Cytectrene are able to cross the BBB regarding there lipophilicity. These characteristic allow them to cross the membrane of the white cells and to be used us a potential agent for the diagnosis of infection. (Author). 44 refs

  6. Radiation protection problems in a laboratory for the labelling of molecules with carbon-11

    International Nuclear Information System (INIS)

    This paper shows that the qualities of carbon-11, especially its short half-life, which suit it so well for the labelling of radiopharmaceuticals prove to be a great handicap in the preparation of these substances. The operator has to make a fresh preparation for each examination and start with strong radioactivities (200 to 500 mCi) in order to obtain an adequate injected activity at the end of the process, the absorbed dose averaging 1.5 man-rem per manipulation at the fingertips. The development of an automatic preparation method involving as little manual interference as possible has halved the collective dose for twice the dose handled. The labelling of molecules used for diagnosis is now considered to take place under satisfactory radioprotection conditions. The fingertip irradiations are analysed in the light of CIPR recommendations, while regretting that in publication 26 this problem of partial external irradiation of the skin is not dealt with as clearly and precisely as before

  7. The use of radioactive cysteine methyl ester for labeling glycosylated molecules oxidized by periodate or neuraminidase plus galactose oxidase

    International Nuclear Information System (INIS)

    Treatment of rat lymph node cells with periodate or neuraminidase plus galactose oxidase initiates blast transformation and cell division of T lymphocytes. Either treatment introduces aldehyde functions onto glycosylated molecules of the plasma membrane. Reduction of the aldehydes with borohydride leads to a concentration-dependent inhibition of the mitogenic response. Cysteine methyl ester (Cys(Me], which can form a stable thiazolidine adduct with aldehydes, also inhibits mitogenesis in a concentration-dependent manner. Maximum inhibition is achieved at Cys(Me) concentrations about 10-fold lower than those required for borohydride (0.4 and 5 mM, respectively). [35S]Cys(Me) has been synthesized and compared with [3H]borohydride as a labeling reagent for molecules on the plasma membrane oxidized by periodate or neuraminidase plus galactose oxidase. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of labeled whole cell lysates or of crude membrane fractions prepared from labeled cells revealed that the same oxidized molecules are specifically labeled with both reagents. Homogenates of cells labeled with either radioactive reagent were fractionated by differential and isopycnic centrifugation. The fractions were analyzed for radioactivity and for a number of marker constituents localized in various subcellular organelles. Following treatment with either reagent, the radioactivity that was covalently incorporated into macromolecules was primarily associated with sedimentable components that distributed among the fractions like plasma membrane markers. When compared with [3H]borohydride, Cys(Me) offers several advantages as a surface labeling reagent for glycosylated plasma membrane molecules, chiefly the possibility of preparing reagents labeled with isotopes other than tritium, including those like 35S, which are much stronger radioactive emitters

  8. Label-free detection of protein molecules secreted from an organ-on-a-chip model for drug toxicity assays

    Science.gov (United States)

    Morales, Andres W.; Zhang, Yu S.; Aleman, Julio; Alerasool, Parissa; Dokmeci, Mehmet R.; Khademhosseini, Ali; Ye, Jing Yong

    2016-03-01

    Clinical attrition is about 30% from failure of drug candidates due to toxic side effects, increasing the drug development costs significantly and slowing down the drug discovery process. This partly originates from the fact that the animal models do not accurately represent human physiology. Hence there is a clear unmet need for developing drug toxicity assays using human-based models that are complementary to traditional animal models before starting expensive clinical trials. Organ-on-a-chip techniques developed in recent years have generated a variety of human organ models mimicking different human physiological conditions. However, it is extremely challenging to monitor the transient and long-term response of the organ models to drug treatments during drug toxicity tests. First, when an organ-on-a-chip model interacts with drugs, a certain amount of protein molecules may be released into the medium due to certain drug effects, but the amount of the protein molecules is limited, since the organ tissue grown inside microfluidic bioreactors have minimum volume. Second, traditional fluorescence techniques cannot be utilized for real-time monitoring of the concentration of the protein molecules, because the protein molecules are continuously secreted from the tissue and it is practically impossible to achieve fluorescence labeling in the dynamically changing environment. Therefore, direct measurements of the secreted protein molecules with a label-free approach is strongly desired for organs-on-a-chip applications. In this paper, we report the development of a photonic crystal-based biosensor for label-free assays of secreted protein molecules from a liver-on-a-chip model. Ultrahigh detection sensitivity and specificity have been demonstrated.

  9. Kinetic and Equilibrium Binding Characterization of Aptamers to Small Molecules using a Label-Free, Sensitive, and Scalable Platform

    OpenAIRE

    Chang, Andrew L.; McKeague, Maureen; Liang, Joe C.; Smolke, Christina D.

    2014-01-01

    Nucleic acid aptamers function as versatile sensing and targeting agents for analytical, diagnostic, therapeutic, and gene-regulatory applications, but their limited characterization and functional validation have hindered their broader implementation. We report the development of a surface plasmon resonance-based platform for rapid characterization of kinetic and equilibrium binding properties of aptamers to small molecules. Our system is label-free and scalable and enables analysis of diffe...

  10. Application of tritiated Schwartz' reagent (ZrCp2Cl3H) for labelling of macrocylic molecules

    International Nuclear Information System (INIS)

    The radiolabelling of macrocycles, such as the immunosuppressant fugimycin, is essential for receptor studies, radioimmuno assays and ADME studies. Through the use of Schwartz' Reagent, ZrCp2Cl3H, it is possible to introduce tritium into the vinylic position of a molecule, a site which is thought to be metabolically stable. The preparation of ZrCp2Cl3H as well as the results on the labelling of simpler model compounds will be discussed

  11. Site-specific labeling of proteins for single-molecule FRET by combining chemical and enzymatic modification

    OpenAIRE

    Jager, M; Nir, E; Weiss, S

    2006-01-01

    An often limiting factor for studying protein folding by single-molecule fluorescence resonance energy transfer (FRET) is the ability to site-specifically introduce a photostable organic FRET donor (D) and a complementary acceptor (A) into a polypeptide chain. Using alternating-laser excitation and chymotrypsin inhibitor 2 as a model, we show that chemical labeling of a unique cysteine, followed by enzymatic modification of a reactive glutamine in an N-terminally appended substrate sequence r...

  12. A Novel Affibody-Auristatin E Conjugate With a Potent and Selective Activity Against HER2+ Cell Lines.

    Science.gov (United States)

    Sochaj-Gregorczyk, Alicja M; Serwotka-Suszczak, Anna M; Otlewski, Jacek

    2016-01-01

    Targeted therapy is a new type of cancer treatment that most often uses biologically active drugs attached to a monoclonal antibody. This so called antibody-drug conjugate strategy allows the use of highly toxic substances that target tumor cells specifically, leaving healthy tissues largely unaffected. Over the last few years, antibody-drug conjugates have become a powerful tool in cancer treatment. We developed and characterized a novel cytotoxic conjugate against HER2 tumors in which the antibody has been substituted with a much smaller molecule: the affibody. The conjugate is composed of the ZHER2:2891 affibody that recognizes HER2 and a highly potent cytotoxic drug auristatin E. The ZHER2:2891 molecule does not contain cysteine(s) in its amino acid sequence. We generated 3 variants of ZHER2:2891, each containing a single cysteine to allow conjugation through the maleimide group that is present in the cytotoxic component. In 2 variants, we introduced single S46C and D53C substitutions. In the third variant, a short Drug Conjugation Sequence (DCS) containing a single cysteine was introduced at the C-terminus of ZHER2:2891, resulting in ZHER2:2891-DCS. The latter variant exhibited a significantly higher conjugation yield, and therefore its cytotoxicity has been studied more thoroughly. The ZHER2:2891-DCS-MMAE conjugate killed the HER2-overexpressing SK-BR-3 and MDA-MB-453 cells efficiently (IC50 values of 5.2 and 24.8 nM, respectively). The T-47-D and MDA-MB-231 cells that express normal levels of HER2 were significantly less sensitive to the conjugate (IC50 values of 135.6 and 161.5 nM, respectively). Overall, we have demonstrated for the first time that proteins other than antibodies/antibody fragments can be successfully combined with a linker-drug module, resulting in conjugates that eliminate cancer cells selectively. PMID:27227324

  13. PLLA-PEG-TCH-labeled bioactive molecule nanofibers for tissue engineering

    Directory of Open Access Journals (Sweden)

    Chen J

    2011-10-01

    Full Text Available Jun Chen1,2, Beth Zhou1–3, Qi Li1,2, Jun Ouyang4, Jiming Kong2,4,5, Wen Zhong3,6, Malcolm MQ Xing1,2,4,71Department of Mechanical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada; 2Manitoba Institute of Child Health, Winnipeg, MB, Canada; 3Department of Textile Sciences, Faculty of Human Ecology, University of Manitoba, Winnipeg, MB, Canada; 4School of Basic Medical Science, Southern Medical University, Guangzhoug, China; 5Department of Human Anatomy and Cell Sciences, 6Department of Medical Microbiology, Faculty of Medicine, 7Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, Winnipeg, MB, CanadaAbstract: By mimicking the native extracellular matrix, electrospun nanofibrous scaffolds (ENSs can provide both chemical and physical cues to modulate cell adherence and differentiation and to promote tissue regeneration while retaining bioresorbable and biocompatible properties. In this study, ENSs were developed to deliver multiple biomolecules by loading them into the core-sheath structure and/or by conjugating them to the nanofiber surfaces. In this work, poly(L-lactide-poly(ethylene glycol-NH2 and poly(L-lactide were emulsion electrospun into nanofibers with a core-sheath structure. A model drug, tetracycline hydrochloride, was loaded within the nanofibers. Amino and carboxyl reactive groups were then activated on the fiber surfaces using saturated water vapor exposure and base hydrolysis, respectively. These reactive groups allowed the surface of the ENS to be functionalized with two other bioactive molecules, fluorescein isothiocyanate- and rhodamine-labeled bovine serum albumins, which were used as model proteins. The ENSs were shown to retain their antimicrobial capacity after two functionalization reactions, indicating that multifunctional nanofibers can potentially be developed into functional wound dressings or periodontal membranes or used in more complicated

  14. Electrochemical immobilization of Fluorescent labelled probe molecules on a FTO surface for affinity detection based on photo-excited current

    Energy Technology Data Exchange (ETDEWEB)

    Haruyama, Tetsuya; Wakabayashi, Ryo; Cho, Takeshi; Matsuyama, Sho-taro, E-mail: haruyama@life.kyutech.as.jp [Kyushu Institute of Technology, Department of Biological Functions and Engineering, Kitakyushu Science and Research Park, Hibikino, Kitakyushu, Fukuoka 808-0196 (Japan)

    2011-10-29

    Photo-excited current can be generated at a molecular interface between a photo-excited molecules and a semi-conductive material in appropriate condition. The system has been recognized for promoting photo-energy devices such as an organic dye sensitized solar-cell. The photo-current generated reactions are totally dependent on the interfacial energy reactions, which are in a highly fluctuated interfacial environment. The authors investigated the photo-excited current reaction to develop a smart affinity detection method. However, in order to perform both an affinity reaction and a photo-excited current reaction at a molecular interface, ordered fabrications of the functional (affinity, photo-excitation, etc.) molecules layer on a semi-conductive surface is required. In the present research, we would like to present the fabrication and functional performance of photo-excited current-based affinity assay device and its application for detection of endocrine disrupting chemicals. On the FTO surface, fluorescent pigment labelled affinity peptide was immobilized through the EC tag (electrochemical-tag) method. The modified FTO produced a current when it was irradiated with diode laser light. However, the photo current decreased drastically when estrogen (ES) coexisted in the reaction solution. In this case, immobilized affinity probe molecules formed a complex with ES and estrogen receptor (ER). The result strongly suggests that the photo-excited current transduction between probe molecule-labelled cyanine pigment and the FTO surface was partly inhibited by a complex that formed at the affinity oligo-peptide region in a probe molecule on the FTO electrode. The bound bulky complex may act as an impediment to perform smooth transduction of photo-excited current in the molecular interface. The present system is new type of photo-reaction-based analysis. This system can be used to perform simple high-sensitive homogeneous assays.

  15. [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551}, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Orlova, Anna; Varasteh, Zohreh [Uppsala University, Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala (Sweden); Hofstroem, Camilla; Graeslund, Torbjoern [Royal Institute of Technology, Division of Molecular Biotechnology, School of Biotechnology, Stockholm (Sweden); Strand, Joanna [Uppsala University, Division of Biomedical Radiation Sciences, Uppsala (Sweden); Sandstrom, Mattias [Uppsala University Hospital, Medical Physics, Department of Oncology, Uppsala (Sweden); Andersson, Karl [Uppsala University, Division of Biomedical Radiation Sciences, Uppsala (Sweden); Ridgeview Instruments AB, Uppsala (Sweden); Tolmachev, Vladimir [Uppsala University, Division of Biomedical Radiation Sciences, Uppsala (Sweden); Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden)

    2013-03-15

    Radionuclide imaging of insulin-like growth factor type 1 receptor (IGF-1R) expression in tumours might be used for selection of patients who would benefit from IGF-1R-targeted therapy. We have previously shown the feasibility of IGF-1R imaging using the Affibody molecule {sup 111}In-DOTA-His{sub 6}-Z{sub IGF1R:4551}. The use of {sup 99m}Tc instead of {sup 111}In should improve sensitivity and resolution of imaging, and reduce the dose burden to patients. We hypothesized that inclusion of a HEHEHE tag instead of a His{sub 6} tag in Z{sub IGF1R:4551} would permit its convenient purification using IMAC, enable labelling with [{sup 99m}Tc(CO){sub 3}]{sup +}, and improve its biodistribution. Z{sub IGF1R:4551} was expressed with a HEHEHE tag in the N terminus. The resulting (HE){sub 3}-Z{sub IGF1R:4551} construct was labelled with [{sup 99m}Tc(CO){sub 3}]{sup +}. Targeting of IGF-1R-expressing cells using [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} was evaluated in vitro and in vivo. (HE){sub 3}-Z{sub IGF1R:4551} was stably labelled with {sup 99m}Tc with preserved specific binding to IGF-1R-expressing DU-145 prostate cancer cells in vitro. In mice, [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} accumulated in IGF-1R-expressing organs (pancreas, stomach, lung and salivary gland). [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} demonstrated 3.6-fold lower accumulation in the liver and spleen than {sup 111}In-DOTA-Z{sub IGF1R:4551}. In NMRI nu/nu mice with DU-145 prostate cancer xenografts, the tumour uptake was 1.32 {+-} 0.11 %ID/g and the tumour-to-blood ratio was 4.4 {+-} 0.3 at 8 h after injection. The xenografts were visualized using a gamma camera 6 h after injection. [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} is a promising candidate for visualization of IGF-1R expression in malignant tumours. (orig.)

  16. Study of acetylcholine and barium receptors in the rat duodeno-jejunum by means of labelled molecules

    International Nuclear Information System (INIS)

    The purpose of this work is the determination of the number and the localization of Acetylcholine and Barium receptors in the rat intestine. We used 'radioactive labelled' drugs to reach a high sensitiveness of detection. So we were able to point out the number of 'effective' molecules of drugs, that is to say the only ones combining with receptors. With the aid of some assumptions, we determine on the one hand the receptors localization by an assessment of the drug penetration depth before reaching their level and on the other hand the number of these receptors. (author)

  17. Labeling of complex molecules with 18F, 13N, and 11C

    International Nuclear Information System (INIS)

    The overall objective during the period covered by this report was to develop a broad spectrum of radiopharmaceuticals labeled with short-lived cyclotron positron emitters, 11C, 13N and 18F. The goals of the program during the last year were: (1) to complete the modular automated system for important precursor production - formaldehyde, methyliodide, cyanide; (2) to perform animal studies with the 18F-glucose analogues 2FDG and 3FDG and measure the constants for both agents in different animals; and (3) to initiate the development of new fatty acid analogues for the myocardial imaging and metabolism. As part of a collaboration with other groups seeking new agents for myocardium and brain, 9-/sup 123m/Te-telluriumheptadecanoic acid as a myocardial imaging agent was studied. This compound could be used for designing new fatty acid analogues labeled with 11C and 18F that stay in the myocardium because of metabolic inhibition

  18. Dextran hydrogel coated surface plasmon resonance imaging (SPRi) sensor for sensitive and label-free detection of small molecule drugs

    Science.gov (United States)

    Li, Shaopeng; Yang, Mo; Zhou, Wenfei; Johnston, Trevor G.; Wang, Rui; Zhu, Jinsong

    2015-11-01

    The label-free and sensitive detection of small molecule drugs on SPRi is still a challenging task, mainly due to the limited surface immobilization capacity of the sensor. In this research, a dextran hydrogel-coated gold sensor chip for SPRi was successfully fabricated via photo-cross-linking for enhanced surface immobilization capacity. The density of the dextran hydrogel was optimized for protein immobilization and sensitive small molecule detection. The protein immobilization capacity of the hydrogel was 10 times greater than a bare gold surface, and 20 times greater than an 11-mercaptoundecanoic acid (MUA) surface. Such a drastic improvement in immobilization capacity allowed the SPRi sensor to detect adequate response signals when probing small molecule binding events. The binding signal of 4 nM liquid-phase biotin to streptavidin immobilized on the dextran surface reached 435 RU, while no response was observed on bare gold or MUA surfaces. The dextran hydrogel-coated SPRi sensor was also applied in a kinetic study of the binding between an immunosuppressive drug (FK506) and its target protein (FKBP12) in a high-throughput microarray format. The measured binding affinity was shown to be consistent with reported literature values, and a detection limit of 0.5 nM was achieved.

  19. Preparation of nanocolloids based on modified DTPA molecule labeled with technetium-99M

    International Nuclear Information System (INIS)

    Full text: The method for preparation of new nanocolloid chemical systems based on modified diethylene triamine pentaacetic acid molecule has been elaborated in this work. Optimal method of sentinel lymph mode detection considers the use of colloid nanomaterials labled with technetium-99m for sintigraphic or radiometric detection of mode localization. The result of dynamic scintigraphic research showed that after being injected the substance is actively accumulated into lymphatic system

  20. Tetrairon(III) single-molecule magnet monolayers on gold: insights from ToF-SIMS and isotopic labeling.

    Science.gov (United States)

    Totaro, Pasquale; Poggini, Lorenzo; Favre, Annaick; Mannini, Matteo; Sainctavit, Philippe; Cornia, Andrea; Magnani, Agnese; Sessoli, Roberta

    2014-07-29

    To work as magnetic components in molecular electronics and spintronics, single-molecule magnets (SMMs) must be reliably interfaced with metals. The organization on gold of a Fe4 SMM carrying two acetyl-protected thiol groups has been studied by exploiting the surface sensitivity of time-of-flight secondary ion mass spectrometry (ToF-SIMS), additionally powered by the use of an isotopic labeling strategy. Deposition from millimolar dichloromethane solutions results in a higher surface coverage and better packed monolayers as compared with previous protocols based on more diluted solutions. Fe4 complexes are chemically tethered to the surface via a single Au-S bond while they still contain an intact SAc group. PMID:25000391

  1. Studies on the development of 99mTc labelled serotonin receptor avid molecules

    International Nuclear Information System (INIS)

    Among the central nervous system (CNS) receptors, serotonin is reported to be very important with respect to the study of brain disorders. Hence this work focuses on serotonin. A summary of the studies that were carried out is given. These include: (a) standardization of the method of serotonin receptor preparation from rat brains and development of a radioreceptor assay using radio-iodinated serotonin, (b) standardization of the method of radio-iodination of serotonin using a tyrosylmethyl ester derivative of serotonin and the preparation of 14C labelled serotonin, (c) synthesis of the SNS tridentate ligand (following the procedure developed by the Democritos National Centre of Scientific Research (NCSR), Athens) and evaluation of a 99mTc complex formed with the tridentate SNS ligand and thiocresol for use as a CNS receptor imaging agent and (d) evaluation of the 99mTc complex formed with a SNS piperazine based tridentate ligand and a monodentate co-ligand (thiophenol obtained from NCSR). This limited study on brain uptake of the complex in rats showed that more structural modification of the ligand is required for preparation of a complex suitable for CNS receptor imaging. Also included is a design for synthesis of a novel complex based on the reported information on the 5-iodo-2-[(2-dimethyl)aminomethylphynoxy]benzyl alcohol compound, which is reported to have a binding affinity for serotonin re-uptake sites. (author)

  2. A laser scanner for imaging fluorophore labeled molecules in electrophoretic gels

    Energy Technology Data Exchange (ETDEWEB)

    Fisk, D.J.; Sutherland, J.C. [Brookhaven National Lab., Upton, NY (United States). Biology Dept.

    1995-08-01

    A laser scanner for imaging electrophoretic gels was constructed and tested. The scanner incorporates a green helium-neon (HeNe) laser (543.5nm wavelength) and can achieve a spatial resolution of 19{micro}m. The instrument can function in two modes : snap-shot and finish-line. In snapshot mode, all samples are electrophoresed for the same time and the gel is scanned after completion of electrophoresis, while in finish-line mode, fluorophore labeled samples are electrophoresed for a constant distance and the image is formed as the samples pass under the detector. The resolving power of the finish-line mode of imaging is found to be greater than that of the snapshot mode of imaging. This laser scanner is also compared with a Charge Coupled Device (CCD) camera and in terms of resolving power is found to be superior. Sensitivity of the instrument is presented in terms of the minimum amount of DNA that can be detected verses its molecular length.

  3. Rapid method for radiofluorination of pyridine derivatives: Prosthetic groups for labelling bioactive molecules

    International Nuclear Information System (INIS)

    Ethyl 2-[18F]fluoro-4-pyridine and ethyl 6-[18F]fluoro-3-pyridine carboxylates were synthesized by catalyzed nucleophlic no-carrier-added radiofluorination. Treatment of the ethyl-2-(N,N,N-trimethylammonium)-4-pyridine- and ethyl-6-(N,N,Ntrimethylammonium)- 3-pyridine carboxylate.treflate precursors with radiofluoride and Kryptofix 2.2.2 in anhydrous acetonitrile at 95 deg. C provided these radiofluorinated intermediates with a greater than 90% radiochemical yield within 2 min reaction time. These intermediates served as precursors to obtain the activated N-succinimidyl 2-[18F]fluoro- 4-pyridine and 6-[18F]fluoro-3-pyridine carboxylate esters for efficient coupling to amine functions in bioactive molecules. This technique was used to radiofluorinate a model chemotactic peptide (N-Formyl-Nle-Leu-Phe-Nle-Tyr-Lys). Biodistribution studies in normal CBA/J mice revealed very rapid clearance through the renal system. (author)

  4. Some examples of the use of carbon 11-labelled molecules in medical research

    International Nuclear Information System (INIS)

    If a radioelement is to be useful for medical diagnosis it must: be an indicator of a normal or pathological biological process; have a half-life consistent with the duration of the biological phenomenon to be observed; emit a suitable radiation. Carbon 11 is one of the radionuclides which best satisfies these different requirements. It is shown how this radioelement, of 20-minute half-life, may be incorporated into psychotropic drugs and biologically useful molecules with enough speed to have an available radioactivity adequate for diagnostic examinations. Two examples are described, one concerning the metabolism of a neuroleptic, chlorpromazine-11C, the other the passage of methionine-11C through the blood brain barrier during a congenital disease, phenylketonuria

  5. Single Molecule 3D Orientation in Time and Space: A 6D Dynamic Study on Fluorescently Labeled Lipid Membranes.

    Science.gov (United States)

    Börner, Richard; Ehrlich, Nicky; Hohlbein, Johannes; Hübner, Christian G

    2016-05-01

    Interactions between single molecules profoundly depend on their mutual three-dimensional orientation. Recently, we demonstrated a technique that allows for orientation determination of single dipole emitters using a polarization-resolved distribution of fluorescence into several detection channels. As the method is based on the detection of single photons, it additionally allows for performing fluorescence correlation spectroscopy (FCS) as well as dynamical anisotropy measurements thereby providing access to fast orientational dynamics down to the nanosecond time scale. The 3D orientation is particularly interesting in non-isotropic environments such as lipid membranes, which are of great importance in biology. We used giant unilamellar vesicles (GUVs) labeled with fluorescent dyes down to a single molecule concentration as a model system for both, assessing the robustness of the orientation determination at different timescales and quantifying the associated errors. The vesicles provide a well-defined spherical surface, such that the use of fluorescent lipid dyes (DiO) allows to establish a a wide range of dipole orientations experimentally. To complement our experimental data, we performed Monte Carlo simulations of the rotational dynamics of dipoles incorporated into lipid membranes. Our study offers a comprehensive view on the dye orientation behavior in a lipid membrane with high spatiotemporal resolution representing a six-dimensional fluorescence detection approach. PMID:26972111

  6. Synthetic and natural consensus design for engineering charge within an affibody targeting epidermal growth factor receptor.

    Science.gov (United States)

    Case, Brett A; Hackel, Benjamin J

    2016-08-01

    Protein ligand charge can impact physiological delivery with charge reduction often benefiting performance. Yet neutralizing mutations can be detrimental to protein function. Herein, three approaches are evaluated to introduce charged-to-neutral mutations of three cations and three anions within an affibody engineered to bind epidermal growth factor receptor. These approaches-combinatorial library sorting or consensus design, based on natural homologs or library-sorted mutants-are used to identify mutations with favorable affinity, stability, and recombinant yield. Consensus design, based on 942 affibody homologs, yielded a mutant of modest function (Kd  = 11 ±4 nM, Tm  = 62°C, and yield = 4.0 ± 0.8 mg/L as compared to 5.3 ± 1.7 nM, 71°C, and 3.5 ± 0.3 mg/L for the parental affibody). Extension of consensus design to 10 additional mutants exhibited varied performance including a substantially improved mutant (Kd  = 6.9 ± 1.4 nM, Tm  = 71°C, and 12.7 ± 0.9 mg/L yield). Sorting a homolog-based combinatorial library of 7 × 10(5) mutants generated a distribution of mutants with lower stability and yield, but did identify one strongly binding variant (Kd  = 1.2 ± 0.3 nM, Tm  = 69°C, and 6.0 ± 0.4 mg/L yield). Synthetic consensus design, based on the amino acid distribution in functional library mutants, yielded higher affinities (P = 0.05) with comparable stabilities and yields. The best of four analyzed clones had Kd  = 1.7 ± 0.5 nM, Tm  = 68°C, and 7.0 ± 0.5 mg/L yield. While all three approaches were effective in creating targeted affibodies with six charged-to-neutral mutations, synthetic consensus design proved to be the most robust. Synthetic consensus design provides a valuable tool for ligand engineering, particularly in the context of charge manipulation. Biotechnol. Bioeng. 2016;113: 1628-1638. © 2016 Wiley Periodicals, Inc. PMID:26724421

  7. Cyclotron production of molecules labelled with short-lived radioisotopes β+ emitters (15O, 13N, 11C) and their clinical uses

    International Nuclear Information System (INIS)

    Clinical use of three short-lived radioisotopes: 15O, 13N and 11C is studied on two complementary aspects. A production and purification system is realized; detection instruments in medical use are studied. The production of labelled molecules with the three radiotracers 15O, 13N, 11C from the target bombardment with charged and accelerated particles was studied

  8. Single molecule resolution of the antimicrobial action of quantum dot-labeled sushi peptide on live bacteria

    Directory of Open Access Journals (Sweden)

    Chen Jianzhu

    2009-05-01

    Full Text Available Abstract Background Antimicrobial peptides are found in all kingdoms of life. During the evolution of multicellular organisms, antimicrobial peptides were established as key elements of innate immunity. Most antimicrobial peptides are thought to work by disrupting the integrity of cell membranes, causing pathogen death. As antimicrobial peptides target the membrane structure, pathogens can only acquire resistance by a fundamental change in membrane composition. Hence, the evolution of pathogen resistance has been a slow process. Therefore antimicrobial peptides are valuable alternatives to classical antibiotics against which multiple drug-resistant bacteria have emerged. For potential therapeutic applications as antibiotics a thorough knowledge of their mechanism of action is essential. Despite the increasingly comprehensive understanding of the biochemical properties of these peptides, the actual mechanism by which antimicrobial peptides lyse microbes is controversial. Results Here we investigate how Sushi 1, an antimicrobial peptide derived from the horseshoe crab (Carcinoscorpius rotundicauda, induces lysis of Gram-negative bacteria. To follow the entire process of antimicrobial action, we performed a variety of experiments including transmission electron microscopy and fluorescence correlation spectroscopy as well as single molecule tracking of quantum dot-labeled antimicrobial peptides on live bacteria. Since in vitro measurements do not necessarily correlate with the in vivo action of a peptide we developed a novel fluorescent live bacteria lysis assay. Using fully functional nanoparticle-labeled Sushi 1, we observed the process of antimicrobial action at the single-molecule level. Conclusion Recently the hypothesis that many antimicrobial peptides act on internal targets to kill the bacterium has been discussed. Here, we demonstrate that the target sites of Sushi 1 are outer and inner membranes and are not cytosolic. Further, our findings

  9. Stable isotope labelling reveals that NaCl stress decreases the production of Ensifer (Sinorhizobium) arboris lipochitooligosaccharide signalling molecules.

    Science.gov (United States)

    Penttinen, Petri; Räsänen, Leena A; Lortet, Gilles; Lindström, Kristina

    2013-12-01

    Ensifer (Sinorhizobium) arboris is a symbiont of salt-tolerant leguminous trees in the genera Acacia and Prosopis that are utilized in the prevention of soil erosion and desertification and in phytoremediation of salinized soil. Signalling between the plant and the rhizobia is essential for the formation of effective symbiosis that increases the success of reclaiming saline sites. We assessed the effect of salt stress on the growth and the production of lipochitooligosaccharide signalling molecules (LCOs) of S. arboris HAMBI 2361, an LCO-overproducing derivative of the S. arboris type strain HAMBI 1552. The strain tolerated NaCl up to 750 mM. To obtain both qualitative and quantitative information on the LCO production under salt stress, we devised a method where LCOs were differentially labelled by stable isotopes of nitrogen, (14)N and (15)N, and analysed by mass spectrometry. Under control conditions, the strain produced altogether 27 structural LCO variants. In 380 mM NaCl, 13 LCO variants were produced in detectable amounts, and six of these were reliably quantified, ranging from one-tenth to one-third of the non-stressed one. PMID:24256411

  10. Immunoassay of 5-methyltetrahydrofolate: use of 125I-labeled protein A as the tracer molecule for specific antibody

    International Nuclear Information System (INIS)

    A sensitive and specific solid-phase radioimmunoassay for 5-methyltetrahydrofolate (5-MTHFA) has been developed. 125I-Labeled staphylococcal Protein A (125I-PA) was used as the tracer molecule for rabbit IgG antibodies bound to 5-MTHFA immobilized on polyacrylamide beads. The dose-dependent inhibition of antibody binding by fluid-phase drug was reflected in decreased binding of 125I-PA. This inhibition, determined in the presence of known amounts of 5-MTHFA, served as the basis for quantification of 5-MTHFA in test samples. An early bleeding was relatively specific; 4.5 ng 5-MTHFA inhibited immune binding by 50% compared to 7700 ng folinic acid or 1200 ng tetrahydrofolate. Other folic acid analogs, including methotrexate, failed to inhibit significantly. The assay using a later bleeding was more sensitive since 1.6 ng 5-MTHFA gave 50% inhibition (detection limit 0.2 ng), but folinic acid cross-reacted significantly. Absorption with immobilized folinic acid markedly enhanced the specificity of this antiserum and resulted in a 15 to 20% increase in maximum inhibition by 5-MTHFA. The assay could be carried out in the presence of 0.025 ml human serum or urine without affecting the standard curve, and was used to determine levels of 5-MTHFA in serum of drug-treated rabbits

  11. Label-free electrochemical lead (II) aptasensor using thionine as the signaling molecule and graphene as signal-enhancing platform.

    Science.gov (United States)

    Gao, Feng; Gao, Cai; He, Suyu; Wang, Qingxiang; Wu, Aiqun

    2016-07-15

    A label-free and highly sensitive electrochemical aptasensor for Pb(2+) was constructed using thionine (TH) as the signaling molecule and graphene (GR) as the signal-enhancing platform. The electrochemical sensing interface was fabricated by stepwise assembly of GR and TH on the lead (II) specific aptamer (LSA) modified electrode. Upon interaction with Pb(2+), the aptamer probe on the sensor underwent conformational switch from a single-stranded DNA form to the G-quadruplex structure, causing the GR with assembled TH released from the electrode surface into solution. As a result, the electrochemical signal of TH on the aptasensor was substantially reduced. Under the optimal experimental conditions, the attenuation of peak currents presented a good linear relationship with the logarithm of Pb(2+) concentrations over the range from 1.6×10(-13) to 1.6×10(-10)M. The detection limit was estimated to be 3.2×10(-14)M. The aptasensor also exhibited good regenerability, excellent selectivity, and acceptable reproducibility, indicating promising application in environment monitoring of lead. PMID:26913503

  12. The tritium labelling of organic molecules by heterogeneous catalytic exchange; El marcado de moleculas organicas con tritio por intercambio catalitico heterogeneo

    Energy Technology Data Exchange (ETDEWEB)

    Angoso Marina, M.; Kaiser Ruiz del Olmo, F.

    1977-07-01

    The influence of the temperature at 65 degree centigree and 120 degree centigree on the labelling of three organic molecules with tritium was studied. The compounds were: benzoic acid, de phenyl glyoxal and 2,3-tetramethylene-4-pantothenyl-7-oxo diacetin.The method employed was the heterogeneous catalytic exchange between tritiated water and the organic compound. The purification was made by thin-layer chromatography and the concentration, purity and specific activity of the products were determined by counting and ultraviolet techniques. The thermal stability and the radiolytic effects on labelled benzoic acid were also considered. (Author) 9 refs.

  13. Enantiospecific C(sp3)-H activation catalyzed by ruthenium nanoparticles : application to isotopic labeling of molecules of biological interest.

    OpenAIRE

    Taglang, Céline

    2015-01-01

    Isotopic labeling with deuterium and tritium is extensively used in chemistry, biology and pharmaceutical research.Numerous methods of labeling by isotopic exchange allow high isotopic enrichments but generally require harsh conditions (high temperatures, acidity). As a consequence, a general, regioselective and smooth labeling method that might be applicable to a wide diversity of substrates remains to develop. In the first part of this thesis, we demonstrated that the use of ruthenium nanop...

  14. A DNA-templated silver nanocluster probe for label-free, turn-on fluorescence-based screening of homo-adenine binding molecules.

    Science.gov (United States)

    Park, Ki Soo; Park, Hyun Gyu

    2015-02-15

    A novel, label-free, turn-on fluorescence strategy to detect molecules that bind to adenine-rich DNA sequences has been developed. The probe employs DNA-templated silver nanoclusters (DNA-AgNCs) as the key detection component. The new strategy relies on the formation of non-Watson-Crick homo-adenine DNA duplex, triggered by strong interactions with homo-adenine binding molecules, which brings a guanine-rich sequence in one strand close to DNA-AgNCs located on the opposite strand. This phenomenon transforms weakly fluorescent AgNCs into highly emissive species that display bright red fluorescence. Finally, we have shown that the new fluorescence turn-on strategy can be employed to detect coralyne, the most representative homo-adenine binding molecule that triggers formation of a non-Watson-Crick homo-adenine DNA duplex. PMID:25441410

  15. Radioiodine and its labelled compounds

    International Nuclear Information System (INIS)

    Chemical characteristics and their nuclear characteristics, types of labelled molecules,labelling procedures, direct labelling with various oxidizing agents, indirect labelling with various conjugates attached to protein molecules, purification and quality control. Iodination damage.Safe handling of labelling procedures with iodine radioisotopes.Bibliography

  16. Analysis of the fluctuations of a single-tethered, quantum-dot labeled DNA molecule in shear flow

    Energy Technology Data Exchange (ETDEWEB)

    Laube, K; Guenther, K; Mertig, M, E-mail: michael.mertig@tu-dresden.de [Professur fuer Physikalische Chemie, Mess- und Sensortechnik, Technische Universitaet Dresden, 01062 Dresden (Germany)

    2011-05-11

    A novel technique for analyzing the conformational fluctuations of a single, surface-tethered DNA molecule by fluorescence microscopy is reported. Attaching a nanometer-sized fluorescent quantum dot to the free end of a {lambda}-phage DNA molecule allows us to study the fluctuations of a native DNA molecule without the mechanical properties being altered by fluorescent dye staining. We report on the investigation of single-tethered DNA in both the unperturbed and the shear flow induced stretched state. The dependence of the observed fractional extension and the magnitude of fluctuations on the shear rate can be qualitatively interpreted by Brochard's stem-and-flower model. The cyclic dynamics of a DNA molecule is directly observed in the shear flow experiment.

  17. The synthesis of multifunctional nanoparticles conjugated with anti-Her2 affibody and monomethylauristatin E

    Science.gov (United States)

    Pala, Katarzyna; Jakimowicz, Piotr; Cyranka-Czaja, Anna; Otlewski, Jacek

    2015-04-01

    Conjugation of bioactive xenobiotics with innert particles often improves their efficacy and/or specificity. In this work we designed superparamagnetic ferric oxide nanoparticles (NPs) conjugated with a strong cytotoxic drug, monomethylauristatin E (MMAE), and evaluated their potential against cancer cells. Cytotoxicity tests showed that the conjugate was at least twice as toxic as the free drug. We then studied the cytotoxic potential of the conjugate at an elevated temperature achieved due to the superparamagnetic properties of the NPs, finding no enhancement of cytotoxicity in comparison with that at 37 °C. Next, multifunctional NPs containing MMAE and a targeting agent were synthesized. The targeting agent was the ZHer2:342 affibody specific to Her2 receptor. The selectivity and effectiveness of the conjugates was evaluated using SK-BR3 (Her2-positive) and U-87 MG (a negative control) cell lines. The multifunctional NPs selectively decrease of the viability of the SK-BR3 cells, showing their specificity towards cells overexpressing the Her2 receptor.

  18. Transport and fate of labelled molecules after application of 14C-gibberellic acid to the young leaves of tomato plants

    International Nuclear Information System (INIS)

    After application of 14C-GA3 to the distal leaflet of young leaves (2.5 cm long) of tomato plants, labelled molecules are exported by the donor leaflet. In the first stage, the transport was basipetal, and preferably took place in the tissues of foliar traces; the tracers moved toward the roots at an average speed greater than 4 cm.h-1. One part of the tracers seemed to accumulate in the elongating internodes, whereas a more important part went into the vessels and then was driven upwards to the leaves by the transpiration stream. A high concentration of tracers was localized in the extremity of some leaflets. The guttated fluid contained labelled molecules having for the most part a Rsub(t) value similar or nearly similar to the Rsub(f) value of GA3 according to the solvent systems. The exportation of 14C, which was at first very low, continued during the development of the donor leaf

  19. Ultra-sensitive DNA assay based on single-molecule detection coupled with fluorescent quantum dot-labeling and its application to determination of messenger RNA

    Energy Technology Data Exchange (ETDEWEB)

    Li Li [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China); Li Xincang [School of Life Sciences, Shandong University, Jinan 250100 (China); Li Lu [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China); Wang Jinxing [School of Life Sciences, Shandong University, Jinan 250100 (China); Jin Wenrui, E-mail: jwr@sdu.edu.cn [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China)

    2011-01-24

    An ultra-sensitive single-molecule detection (SMD) method for quantification of DNA using total internal reflection fluorescence microscopy (TIRFM) coupled with fluorescent quantum dot (QD)-labeling was developed. In this method, the target DNA (tDNA) was captured by the capture DNA immobilized on the silanized coverslip blocked with ethanolamine and bovine serum albumin. Then, the QD-labeled probe DNA was hybridized to the tDNA. Ten fluorescent images of the QD-labeled sandwich DNA hybrids on the coverslip were taken by a high-sensitive CCD. The tDNA was quantified by counting the bright spots on the images using a calibration curve. The LOD of the method was 1 x 10{sup -14} mol L{sup -1}. Several key factors, including image acquirement, fluorescence probe, substrate preparation, noise elimination from solutions and glass coverslips, and nonspecific adsorption and binding of solution-phase detection probes were discussed in detail. The method could be applied to quantify messenger RNA (mRNA) in cells. In order to determine mRNA, double-stranded RNA-DNA hybrids consisting of mRNA and corresponding cDNA were synthesized from the cellular mRNA template using reverse transcription in the presence of reverse transcriptase. After removing the mRNA in the double-stranded hybrids using ribonuclease, cDNA was quantified using the SMD-based TIRFM. Osteopontin mRNA in decidual stromal cells was chosen as the model analyte.

  20. Enantio-specific C(sp3)-H activation catalyzed by ruthenium nanoparticles: application to isotopic labeling of molecules of biological interest

    International Nuclear Information System (INIS)

    Isotopic labeling with deuterium and tritium is extensively used in chemistry, biology and pharmaceutical research. Numerous methods of labeling by isotopic exchange allow high isotopic enrichments but generally require harsh conditions (high temperatures, acidity). As a consequence, a general, regioselective and smooth labeling method that might be applicable to a wide diversity of substrates remains to develop. In the first part of this thesis, we demonstrated that the use of ruthenium nanoparticles, synthesized by Pr. Bruno Chaudret's team (INSA Toulouse), allowed the mild (2 bar of deuterium gas at 55 C), effective and selective H/D exchange reaction of a large variety of nitrogen-containing compounds, such as pyridines, indoles and primary, secondary and tertiary alkyl amines. The usefulness and the efficiency of this novel methodology was demonstrated by the deuteration of eight nitrogen-containing molecules of biological interest without altering their chemical and stereochemical properties. However, the conservation of the original stereochemistry of an activated chiral C-H center remains a major issue. We studied the reactivity of RuNP(at)PVP on different categories of nitrogen-containing substrates (amines, aminoacids and peptides) in water or in organic solvents. Our results showed that C-H activation of chiral carbons C(sp3) took place efficiently, selectively and, in all cases, with total retention of configuration. The wide range of applications of this procedure was demonstrated by the labeling of three chiral amines, fourteen aminoacids, three aromatic amino esters and four peptides. Moreover, our collaboration with Pr. Romuald Poteau's team (INSA Toulouse) led to the identification of two mechanisms by ab initio simulation in agreement with our experimental results: the σ-bond metathesis mechanism and the oxidative addition mechanism. These two mechanisms imply two vicinal ruthenium atoms leading to the formation an original

  1. Screening small-molecule compound microarrays for protein ligands without fluorescence labeling with a high-throughput scanning microscope

    OpenAIRE

    Fei, Yiyan; Landry, James P.; Sun, Yungshin; Zhu, Xiangdong; Wang, Xiaobing; Luo, Juntao; Wu, Chun-Yi; Lam, Kit S.

    2010-01-01

    We describe a high-throughput scanning optical microscope for detecting small-molecule compound microarrays on functionalized glass slides. It is based on measurements of oblique-incidence reflectivity difference and employs a combination of a y-scan galvometer mirror and an x-scan translation stage with an effective field of view of 2 cm×4 cm. Such a field of view can accommodate a printed small-molecule compound microarray with as many as 10,000 to 20,000 targets. The scanning microscope is...

  2. Single molecule super-resolution imaging of proteins in living Salmonella enterica using self-labelling enzymes.

    Science.gov (United States)

    Barlag, Britta; Beutel, Oliver; Janning, Dennis; Czarniak, Frederik; Richter, Christian P; Kommnick, Carina; Göser, Vera; Kurre, Rainer; Fabiani, Florian; Erhardt, Marc; Piehler, Jacob; Hensel, Michael

    2016-01-01

    The investigation of the subcellular localization, dynamics and interaction of proteins and protein complexes in prokaryotes is complicated by the small size of the cells. Super-resolution microscopy (SRM) comprise various new techniques that allow light microscopy with a resolution that can be up to ten-fold higher than conventional light microscopy. Application of SRM techniques to living prokaryotes demands the introduction of suitable fluorescent probes, usually by fusion of proteins of interest to fluorescent proteins with properties compatible to SRM. Here we describe an approach that is based on the genetically encoded self-labelling enzymes HaloTag and SNAP-tag. Proteins of interest are fused to HaloTag or SNAP-tag and cell permeable substrates can be labelled with various SRM-compatible fluorochromes. Fusions of the enzyme tags to subunits of a type I secretion system (T1SS), a T3SS, the flagellar rotor and a transcription factor were generated and analysed in living Salmonella enterica. The new approach is versatile in tagging proteins of interest in bacterial cells and allows to determine the number, relative subcellular localization and dynamics of protein complexes in living cells. PMID:27534893

  3. Mineralization of 14C-labelled aromatic pesticide molecules in Egyptian soils under aerobic and anaerobic conditions

    International Nuclear Information System (INIS)

    The mineralization of 2,4-D, carbofuran and pirimiphos-methyl in Egyptian soils was studied over a period of 90 days. Laboratory studies under aerobic and anaerobic conditions were conducted using 14C-ring labelled pesticides. Under anaerobic conditions 10-14% of applied ring labelled 2,4-D mineralized during 90 days with no significant variations due to soil type. Under aerobic conditions, 2,4-D mineralized more readily in clay soil to reach 29-34% of applied dose within 90 days. In clay loam soil, 14C-carbofuran and 14C-pirimiphos-methyl mineralized at a rather slow rate to reach 12-14% and 12-13% of applied dose in 90 days, respectively under aerobic conditions. Generally, soils repeatedly treated with pesticides gave a slightly lower percentage of mineralization than control soils. In all studies, the soil extractable pesticide residues decreased with time and the bound residues gradually increased. The highest binding affinity of about 26-29% was observed with 2,4-D in clay soil under aerobic conditions in 90 days. Carbofuran, and pirimiphos-methyl, on the other hand, had lower binding capacity that did not exceed 16% of applied radioactivity. (author)

  4. Label-free liquid crystal biosensor for L-histidine: A DNAzyme-based platform for small molecule assay.

    Science.gov (United States)

    Liao, Shuzhen; Ding, Huazhi; Wu, Yan; Wu, Zhaoyang; Shen, Guoli; Yu, Ruqin

    2016-05-15

    We have developed a novel DNAzyme-based liquid crystal (LC) biosensor with high sensitivity for L-histidine, which is based on L-histidine-mediated formation of DNA duplexes by cleaving DNAzyme using L-histidine, resulting in a remarkable optical signal. Firstly, an optimal amount of capture probe is bound to the glass slide, which changes the surface topology as little as possible and shows a zero-background for the sensing system. When the DNAzyme molecule is cleaved by the target, L-histidine, a partial substrate strand is produced, which in turn can hybridize with the capture probe, forming a DNA duplex. The DNA duplexes induce LC molecules to undergo a homeotropic-to-tiled transition, obtaining a remarkable optical signal. The results show that the DNAzyme-based LC biosensor is highly sensitive to L-histidine with a detection limit of 50nM. Compared with previously reported multi-step amplified methods, this newly designed assay system for L-histidine has no amplified procedures with comparable sensitivity. This method is an unprecedented example of DNAzyme-based LC biosensor for small molecules, which has potential to offer a DNAzyme-based LC model used in various targets. PMID:26765528

  5. Labeling of complex molecules with 18F, 13N, and 11C. Progress report, March 1, 1981-February 28, 1982

    International Nuclear Information System (INIS)

    The overall objective during the period covered by this report was to develop a broad spectrum of radiopharmaceuticals labeled with short-lived cyclotron produced positron emitters, 11C, 13N and 18F. The progress report of this year will summarize work done in the last three years. The goals of the program during the last three years were: to build and complete the transport system to Nuclear Medicine; to complete the modular automated system for important precursor production: formaldehyde, methyliodide, cyanide; to perform animal studies with the 18F-glucose analogs 2FDG and 3FDG and measure the rate constants and glucose metabolic rates derived from the Sokoloff model for both agents in different animal species; to initiate the development of new fatty acid analogs for myocardial imaging and metabolism; and to develop syntheses for 18F and 11C sugar analogs

  6. Expression profile of vascular cell adhesion molecule-1 (CD106) in inflammatory foci using rhenium-188 labelled monoclonal antibody in mice.

    Science.gov (United States)

    Kairemo, K J; Strömberg, S; Nikula, T K; Karonen, S L

    1998-06-01

    Rhenium (Re)-188 is a generator (W-188/Re-188) produced high energy beta-emitter suitable for radionuclide therapy (T1/2 is 16.9 hrs and Emax 2.1 MeV (range 11 mm)). We have labelled monoclonal antibody (MAb) raised against vascular cell adhesion molecule-1 (VCAM-1) with Re-188 using glucoheptonate chelation technique and SnCl2 as reducing agent. The labelling efficiency, free perrhenate and reduced Re were controlled with thin layer chromatography and the purification of Re-188-MoAbs was performed using gel filtration. Our results indicate that Re-188-labelled antibodies remain in vitro stable and the labelling purity is > 90%. We also have applied these Re-188-MoAbs for detection of inflammatory disease in a mouse. The effective half-lives of organs of interest after an injection of Re-188-anti-VCAM1 were as follows: blood 5.2 hr, kidney 4.7 hr, and liver 9.6 hr. Re-188-anti-VCAM-1 was found to accumulate mainly in kidney and liver. One hour after the injection, the kidney contained in average as high as 12.5% and the liver 2.8 ID/g tissue. After 6 hr, the kidney contained 5.5% ID/g and the liver 2.6% ID/g. At 24 hr, the kidney uptake was 0.5% ID/g and the liver uptake 0.8% ID/g, respectively. The inflamed foci, subcutaneous lesions in the footpad skin, were visualized using gamma camera. From the distribution data the uptakes in the inflamed foci as follows: at 1 hr 2.18 (inflammation) and 1.72% ID/g (control), at 6 hr 1.42 (inflammation) and 0.85% ID/g (control), and at 24 hr 0.17 (inflammation) and 0.084% ID/g (control), respectively. Anti-VCAM-1 MAb showed better targeting as compared to control MoAbs in inflammation (caused by E.coli lipoplysaccaride). In conclusion, Re-188 is suitable for MAb labelling, and MAb against VCAM-1 may be used for detection of local inflammatory disease. PMID:9762472

  7. Direct and in vitro observation of growth hormone receptor molecules in A549 human lung epithelial cells by nanodiamond labeling

    Science.gov (United States)

    Cheng, C.-Y.; Perevedentseva, E.; Tu, J.-S.; Chung, P.-H.; Cheng, C.-L.; Liu, K.-K.; Chao, J.-I.; Chen, P.-H.; Chang, C.-C.

    2007-04-01

    This letter presents direct observation of growth hormone receptor in one single cancer cell using nanodiamond-growth hormone complex as a specific probe. The interaction of surface growth hormone receptor of A549 human lung epithelial cells with growth hormone was observed using nanodiamond's unique spectroscopic signal via confocal Raman mapping. The growth hormone molecules were covalent conjugated to 100nm diameter carboxylated nanodiamonds, which can be recognized specifically by the growth hormone receptors of A549 cell. The Raman spectroscopic signal of diamond provides direct and in vitro observation of growth hormone receptors in physiology condition in a single cell level.

  8. Chelator-Accelerated One-Pot ‘Click’ Labeling of Small Molecule Tracers with 2-[18F]Fluoroethyl Azide

    Directory of Open Access Journals (Sweden)

    Erik Årstad

    2013-05-01

    Full Text Available 2-[18F]Fluoroethyl azide ([18F]FEA can readily be obtained by nucleophilic substitution of 2-azidoethyl-4-toluenesulfonate with [18F]fluoride (half-life 110 min, and has become widely used as a reagent for ‘click’ labeling of PET tracers. However, distillation of [18F]FEA is typically required, which is time-consuming and unpractical for routine applications. In addition, copper(I-catalyzed cycloaddition of [18F]FEA with non-activated alkynes, and with substrates containing labile functional groups, can be challenging. Herein, we report a highly efficient and practical ligand-accelerated one-pot/two-step method for ‘click’ labeling of small molecule tracers with [18F]FEA. The method exploits the ability of the copper(I ligand bathophenanthrolinedisulfonate to accelerate the rate of the cycloaddition reaction. As a result, alkynes can be added directly to the crude reaction mixture containing [18F]FEA, and as cyclisation occurs almost immediately at room temperature, the reaction is tolerant to labile functional groups. The method was demonstrated by reacting [18F]FEA with a series of alkyne-functionalized 6-halopurines to give the corresponding triazoles in 55–76% analytical radiochemical yield.

  9. Determination of human IgG by solid substrate room temperature phosphorescence immunoassay based on an antibody labeled with nanoparticles containing Rhodamine 6G luminescent molecules

    Science.gov (United States)

    Jia-Ming, Liu; hui, Zhu Guo; Aihong, Wu; Pingping, Li; Huanhuan, Xu; Li, Long-Di; Liu, Zhen-bo

    2005-03-01

    Luminescent silicon dioxide nanoparticles (R-SiO 2) with size of 50 nm containing Rhodamine 6G (R) were synthesized by sol-gel method. In the presence of Pb(Ac) 2 as a heavy atom perturber, the particle can emit intense and stable room temperature phosphorescence signal of R, respectively, on polyamide membrane, with the λexmax/λemmax=470/635 nm for R. Our research indicates that the specific immune reaction between goat-anti-human IgG antibody labeled with R-SiO 2 and human IgG can be carried on polyamide membrane quantitatively, and the phosphorescence intensity was enhanced after the immunoreactions. Thus, a new method of solid substrate room temperature phosphorescence immunoassay (SS-RTP-IA) for the determination of human IgG was established basing on antibody labeled with the nanoparticles containing binary luminescent molecules. The linear range of this method is 0.0624-20.0 pg spot -1 of human IgG (corresponding concentration, 0.156-50.0 ng mL -1; sample volume, 0.40 μL spot -1). The regression equations of working curves are Δ Ip = 88.16. + 16.79m IgG (pg spot -1) (485/646 nm, r = 0.9997). Detection limits calculated by 3Sb/k are 0.017 pg spot -1. For samples containing 0.156 and 50.0 ng mL -1 of IgG, we measured repeatedly for 11 times, RSDs are 3.9 and 2.8%, respectively. This method is sensitive, accurate and of high precision.

  10. Targeting, bio distributive and tumor growth inhibiting characterization of anti-HER2 affibody coupling to liposomal doxorubicin using BALB/c mice bearing TUBO tumors.

    Science.gov (United States)

    Akhtari, Javad; Rezayat, Seyed Mahdi; Teymouri, Manouchehr; Alavizadeh, Seyedeh Hoda; Gheybi, Fatemeh; Badiee, Ali; Jaafari, Mahmoud Reza

    2016-05-30

    Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-30% of breast cancer tumors. In the current investigation, we exploited such a feature and utilized an anti-HER2 affibody (ZHER2:477) in combination with a pegylated liposomal doxorubicin (PLD) for concurrent passive and active targeting of HER2 overexpressing TUBO tumor, using BALB/c mice. It was determined that the affibody coupled liposomes (affisomes) was capable of increasing doxorubicin (Dox) delivery to HER2+ cells (SK-BR-3 and TUBO cells), while transferring drug similarly as low as naïve PLD to HER2- MDA-MB-231 cells. This also resulted in selectively enhance cytotoxicity. The veracity of targeting was further assessed utilizing DiD lipophilic tracer model liposomes via competition assay. An approximated 10 ligand/liposome integration caused Dox delivery at 50% of maximal delivery capacity (Kd). Such integration did not alter Dox release in vitro, while it affected the serum clearance profile. Affibody integration to PLD increased drug concentration in tumor and led to significantly further augmentation of drug in liver and spleen compared to those of PLD. Overall, such differences led to prolonging the mice life spans as compared to PLD. PMID:27039149

  11. Novel Chemical Strategies for Labeling Small Molecule Ligands for Androgen, Progestin, and Peroxisome Proliferator-Activated Receptors for Imaging Prostate and Breast Cancer and the Heart

    International Nuclear Information System (INIS)

    Summary of Progress The specific aims of this project can be summarized as follows: Aim 1: Prepare and evaluate radiolabeled ligands for the peroxisome proliferator-activated receptor γ (PPARγ), a new nuclear hormone receptor target for tumor imaging and hormone therapy. Aim 2: Prepare steroids labeled with a cyclopentadienyl tricarbonyl technetium or rhenium unit. Aim 3: Prepare and evaluate other organometallic systems of novel design as ligand mimics and halogenated ligands for nuclear hormone receptor-based tumor imaging. As is described in detail in the report, we made excellent progress on all three of these aims; the highlights of our progress are the following: (1) we have prepared the first fluorine-18 labeled analogs of ligands for the PPARγ receptor and used these in tissue distribution studies in rats; (2) we have developed three new methods for the synthesis of cyclopentadienyltricarbonyl rhenium and technetium (CpRe(CO)3 and CpTc(CO)3) systems and we have adapted these to the synthesis of steroids labeled with these metals, as well as ligands for other receptor systems; (3) we have prepared a number of fluorine-18 labeled steroidal and non-steroidal androgens and measured their tissue distribution in rats; (4) we have prepared iodine and bromine-labeled progestins with high progesterone receptor binding affinity; and (5) we have prepared inorganic metal tricarbonyl complexes and steroid receptor ligands in which the metal tricarbonyl unit is an integral part off the ligand core

  12. Food Labels

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Food Labels KidsHealth > For Teens > Food Labels Print A ... have at least 95% organic ingredients. continue Making Food Labels Work for You The first step in ...

  13. Preparation, characterization and magnetic behavior of a spin-labelled physical hydrogel containing a chiral cyclic nitroxide radical unit fixed inside the gelator molecule.

    Science.gov (United States)

    Takemoto, Yusa; Yamamoto, Takayuki; Ikuma, Naohiko; Uchida, Yoshiaki; Suzuki, Katsuaki; Shimono, Satoshi; Takahashi, Hiroki; Sato, Nobuhiro; Oba, Yojiro; Inoue, Rintaro; Sugiyama, Masaaki; Tsue, Hirohito; Kato, Tatsuhisa; Yamauchi, Jun; Tamura, Rui

    2015-07-21

    An optically active amphiphilic nitroxide radical compound [(S,S,R)-], which contains a paramagnetic (2S,5S)-2,5-dimethyl-2,5-diphenylpyrrolidine-N-oxyl radical group fixed in the inner position together with a hydrophobic long alkyl chain and a hydrophilic (R)-alanine residue in the opposite terminal positions, was found to serve as a low-molecular-weight gelator in H2O to give rise to a spin-labelled physical hydrogel. Characterization of the hydrogel was performed by microscopic (SEM, TEM and AFM) techniques, XRD and SAXS measurements, and IR, UV and CD spectroscopies. The gel-sol transition temperature was determined by EPR spectral line-width (ΔHpp) analysis. Measurement of the temperature dependence of relative paramagnetic susceptibility (χrel) for the hydrogel and sol phases was achieved by means of the double-integration of VT-EPR spectra. PMID:26073537

  14. Determination of human IgG by solid substrate room temperature phosphorescence immunoassay based on an antibody labeled with nanoparticles containing dibromofluorescein luminescent molecules

    International Nuclear Information System (INIS)

    Luminescent silicon dioxide nano-particles with size of 20 nm, which containing dibromofluorescein (D) were synthesized by sol-gel method (symbolized by D-SiO2).The particles can emit intense and stable room temperature phosphorescence signal on polyamide membrane when Pb(Ac)2 was used as a heavy atom perturber. The λexmax/λemmax was 457/622 nm. Our research indicated that the specific immune reaction between goat-anti-human IgG antibody labeled with D-SiO2 and human IgG could be carried out on polyamide membrane quantitatively, and the phosphorescence intensity of the particle was enhanced after the immunoreactions. Thus a new method of solid substrate room temperature phosphorescence immunoassay (SS-RTP-IA) for the determination of human IgG was established basing on antibody labeled with the D-SiO2 nanoparticles. The linear range of this method was 0.0624-20.0 pg human IgG spot-1 (corresponding concentration: 0.156-50.0 ng ml-1, the sample volume: 0.40 μl spot-1) with a limit of detection (LD) as 0.018 pg spot-1, and the regression equation of working curve was ΔIp = 7.201 mIgG (pg spot-1) + 82.57. Samples containing 0.156 and 50.0 ng ml-1 of IgG were measured repeatedly for 11 times and R.S.D.s were 4.1 and 3.4%, respectively. Results showed that this method had the merits as sensitive, accurate and precise

  15. Radiation dosimetry and first therapy results with a {sup 124}I/{sup 131}I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zechmann, Christian M.; Afshar-Oromieh, Ali; Mier, Walter [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Armor, Tom; Joyal, John [Molecular Insight Pharmaceuticals, Boston, MA (United States); Stubbs, James B. [Radiation Dosimetry Systems RDS, Inc., Apharetta, GA (United States); Hadaschik, Boris [University Hospital Heidelberg, Department of Urology, Heidelberg (Germany); Kopka, Klaus [Division Radiopharmaceutical Chemistry, DKFZ, Heidelberg (Germany); Debus, Juergen [University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Babich, John W. [Molecular Insight Pharmaceuticals, Boston, MA (United States); Cornell University, Division of Radiopharmacy, Department of Radiology, New York, NY (United States); Haberkorn, Uwe [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Clinical Cooperation Unit Nuclear Medicine, DKFZ, Heidelberg (Germany)

    2014-07-15

    Since the prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) several PSMA-targeting molecules are under development to detect and treat metastatic castration resistant prostate cancer (mCRPC). We investigated the tissue kinetics of a small molecule inhibitor of PSMA ((S)-2-(3-((S)-1-carboxy-5-(3-(4-[{sup 124}I]iodophenyl)ureido)pentyl)ureido) pentan edioicacid; MIP-1095) using PET/CT to estimate radiation dosimetry for the potential therapeutic use of {sup 131}I-MIP-1095 in men with mCRPC. We also report preliminary safety and efficacy of the first 28 consecutive patients treated under a compassionate-use protocol with a single cycle of {sup 131}I-MIP-1095. Sixteen patients with known prostate cancer underwent PET/CT imaging after i.v. administration of {sup 124}I-MIP-1095 (mean activity: 67.4 MBq). Each patient was scanned using PET/CT up to five times at 1, 4, 24, 48 and 72 h post injection. Volumes of interest were defined for tumor lesions and normal organs at each time point followed by dose calculations using the OLINDA/EXM software. Twenty-eight men with mCRPC were treated with a single cycle of {sup 131}I-MIP-1095 (mean activity: 4.8 GBq, range 2 to 7.2 GBq) and followed for safety and efficacy. Baseline and follow up examinations included a complete blood count, liver and kidney function tests, and measurement of serum PSA. I-124-MIP-1095 PET/CT images showed excellent tumor uptake and moderate uptake in liver, proximal intestine and within a few hours post-injection also in the kidneys. High uptake values were observed only in salivary and lacrimal glands. Dosimetry estimates for I-131-MIP-1095 revealed that the highest absorbed doses were delivered to the salivary glands (3.8 mSv/MBq), liver (1.7 mSv/MBq) and kidneys (1.4 mSv/MBq). The absorbed dose calculated for the red marrow was 0.37 mSv/MBq. PSA values decreased by >50 % in 60.7 % of the men treated. Of men with bone pain, 84.6 % showed complete or

  16. Wasteful Labeling

    OpenAIRE

    Mahenc, Philippe

    2009-01-01

    The role of labeling is to solve the adverse selection problem caused by unsubstantiated claims from firms. The problem however is likely to remain unsolved if the labeling agency is not trustworthy.The agency can be suspected to divert the fees charged for labeling from their primary purpose of collecting information in order to raise excessive revenue. This paper addresses this issue and shows that labeling may be wasteful if the agency is likely to be untrustworthy. To award firms green la...

  17. Label and Label-Free Detection Techniques for Protein Microarrays

    Directory of Open Access Journals (Sweden)

    Amir Syahir

    2015-04-01

    Full Text Available Protein microarray technology has gone through numerous innovative developments in recent decades. In this review, we focus on the development of protein detection methods embedded in the technology. Early microarrays utilized useful chromophores and versatile biochemical techniques dominated by high-throughput illumination. Recently, the realization of label-free techniques has been greatly advanced by the combination of knowledge in material sciences, computational design and nanofabrication. These rapidly advancing techniques aim to provide data without the intervention of label molecules. Here, we present a brief overview of this remarkable innovation from the perspectives of label and label-free techniques in transducing nano‑biological events.

  18. Nutrition Labeling

    DEFF Research Database (Denmark)

    Grunert, Klaus G

    2013-01-01

    because consumers will avoid products that the label shows to be nutritionally deficient, but also because food producers will try to avoid marketing products that appear, according to the label, as nutritionally problematic, for example, because of a high content of saturated fat or salt. Nutrition......Nutrition labeling refers to the provision of information on a food product’s nutritional content on the package label. It can serve both public health and commercial purposes. From a public health perspective, the aim of nutrition labeling is to provide information that can enable consumers...... to make healthier choices when choosing food products. Nutrition labeling is thus closely linked to the notion of the informed consumer, that chooses products according to their aims, on the basis of the information at their disposal. Because many consumers are assumed to be interested in making healthy...

  19. Nutrition Labeling

    Science.gov (United States)

    Metzger, Lloyd E.

    Nutrition labeling regulations differ in countries around the world. The focus of this chapter is on nutrition labeling regulations in the USA, as specified by the Food and Drug Administration (FDA) and the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA). A major reason for analyzing the chemical components of foods in the USA is nutrition labeling regulations. Nutrition label information is not only legally required in many countries, but also is of increasing importance to consumers as they focus more on health and wellness.

  20. Expression of apoptotic nuclei by ultrastructural terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling and detection of FasL, caspases and PARP protein molecules in cadmium induced acute alveolar cell injury

    International Nuclear Information System (INIS)

    Cadmium causes cellular damage but the exact mechanism of apoptosis in cadmium induced acute lung injury is not clear. We investigated the sequential expression of apoptotic nuclei and detected related molecules in tissue of cadmium-induced acute lung injury. Forty Sprague-Dawley rats were sacrificed at days 1, 3, 7 and 10 after intra-tracheal cadmium injection (2.5 mg/kg). Light microscopic, ultrastructural terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling (TUNEL), and Western blot analysis for detection of FasL, Bid, cytochrome c, caspase 3 and PARP were carried out. Apoptosis occurred at day 1, and markedly decreased at days 3, 7 and 10 (11.8, 2.8, 0.9, 0.5%, respectively) determined by light microscopy and TUNEL assay. Ultrastructural TUNEL revealed two patterns of nuclear morphology according to the apoptotic stage. One pattern showed chromatin fragmentation and apoptotic nuclear body formation. The other pattern had bleb formation in the chromatin, budding with projection out to the nuclear membranes, fragmentation, segregation of chromatin clumps and apoptotic body formation. Western blot analysis showed prominent expression of FasL at days 1 and 3. Expression of Bid, cytochrome c and caspase 3 were prominent at day 1 compared to days 3, 7 and 10. PARP cleavage was prominent at day 1. In conclusion, intra-tracheal cadmium injection showed active alveolar cell apoptosis at day 1. Ultrastructural TUNEL showed various expressions according to the apoptotic nuclear stage. These studies suggest that cadmium-induced alveolar cell apoptosis is mediated by FasL and caspase-dependent mitochondrial apoptosis pathways

  1. Atoms, molecules & elements

    CERN Document Server

    Graybill, George

    2007-01-01

    Young scientists will be thrilled to explore the invisible world of atoms, molecules and elements. Our resource provides ready-to-use information and activities for remedial students using simplified language and vocabulary. Students will label each part of the atom, learn what compounds are, and explore the patterns in the periodic table of elements to find calcium (Ca), chlorine (Cl), and helium (He) through hands-on activities.

  2. Protein aggregation and degradation during iodine labeling and its consequences for protein adsorption to biomaterials

    DEFF Research Database (Denmark)

    Holmberg, Maria; Jensen, Karin Bagger Stibius; Ndoni, Sokol;

    2007-01-01

    the CAT method, and higher amounts of fragmentation are observed for CAT-labeled IgG molecules relative to unlabeled IgG molecules as well as to IgG molecules labeled using the Iodo-Gen method. These results show that the widely applied method of radioisotope labeling for quantitative assessment of...

  3. Radioactively labelled porphyrin derivatives

    International Nuclear Information System (INIS)

    Radioactive labelling of guanidine bearing tetraphenylporphyrin and Dy-texaphyrin with 166Ho and 90Y is described. UV-VIS absorption spectrometry was used to describe porphyrin and texaphyrin, including their behaviour over a wide pH range. This technique also provided preliminary information about the complexation of holmium and yttrium with porphyrin and texaphyrin. The labelling yield of the macrocyclic molecules depends on the pH of the reaction mixture, metal-to-ligand ratio and time of incubation. The optimum reaction conditions for the formation of radioactive complexes of porphyrin and texaphyrin were determined by thin layer chromatography combined with beta activity measurement. The ability of porphyrin derivatives to bind anions was also examined. Our experiments were focused on perrhenate ion (ReO4-) because radiopharmaceuticals labeled with 186Re and 188Re play an important role in the therapy of many tumorous diseases. The possibility of using the ReO4- anion directly for labeling without reduction to a lower oxidation state can simplify considerably the preparation of the radiotherapeutic pharmaceuticals. Neither UV-Vis spectrometry nor TLC gave evidence of any incorporation of the ReO4- anion into the porphyrin ring

  4. A small-molecule dye for NIR-II imaging

    Science.gov (United States)

    Antaris, Alexander L.; Chen, Hao; Cheng, Kai; Sun, Yao; Hong, Guosong; Qu, Chunrong; Diao, Shuo; Deng, Zixin; Hu, Xianming; Zhang, Bo; Zhang, Xiaodong; Yaghi, Omar K.; Alamparambil, Zita R.; Hong, Xuechuan; Cheng, Zhen; Dai, Hongjie

    2016-02-01

    Fluorescent imaging of biological systems in the second near-infrared window (NIR-II) can probe tissue at centimetre depths and achieve micrometre-scale resolution at depths of millimetres. Unfortunately, all current NIR-II fluorophores are excreted slowly and are largely retained within the reticuloendothelial system, making clinical translation nearly impossible. Here, we report a rapidly excreted NIR-II fluorophore (~90% excreted through the kidneys within 24 h) based on a synthetic 970-Da organic molecule (CH1055). The fluorophore outperformed indocyanine green (ICG)--a clinically approved NIR-I dye--in resolving mouse lymphatic vasculature and sentinel lymphatic mapping near a tumour. High levels of uptake of PEGylated-CH1055 dye were observed in brain tumours in mice, suggesting that the dye was detected at a depth of ~4 mm. The CH1055 dye also allowed targeted molecular imaging of tumours in vivo when conjugated with anti-EGFR Affibody. Moreover, a superior tumour-to-background signal ratio allowed precise image-guided tumour-removal surgery.

  5. Photoisomerisable molecules

    OpenAIRE

    Peris Fajarnes, Eduardo Víctor; Mata Martínez, José Antonio; Márquez Linares, Francisco Manuel; Sabater Picot, María José

    2005-01-01

    [EN] The invention relates to a molecule comprising at least one carbon-carbon double bond which is substituted by at least one cyclopentadienyl-metal-cyclopentadienyl complex, having the cis/trans isomerisation property, in a reversible manner in response to the absorption of light. Preferably, the rest of the molecule comprises a dendrimer of any generation, advantageously of the polypropylenimine octaamine type. The inventive molecule can be used as a molecular switch and in various differ...

  6. Food labels

    DEFF Research Database (Denmark)

    Selsøe Sørensen, Henrik; Clement, Jesper; Gabrielsen, Gorm

    2012-01-01

    The food industry develops tasty and healthy food but fails to deliver the message to all consumers. The consumers’ background knowledge is essential for how they find and decode relevant elements in the cocktail of signs which fight for attention on food labels. In this exploratory study, we find...... evidence for dividing consumers into two profiles: one relying on general food knowledge and another using knowledge related to signpost labels. In a combined eyetracking and questionnaire survey we analyse the influence of background knowledge and identify different patterns of visual attention for the...... two consumer profiles. This underlines the complexity in choosing and designing the ‘right’ elements for a food package that consumers actually look at and are able to make rational use of. In spite of any regulation of food information provided by authorities, consumers will still be confronted with...

  7. Environmental Labeling

    OpenAIRE

    Andrea Podhorsky

    2009-01-01

    This paper studies how information disclosed by voluntary environmental labels creates incentives for firms to invest in environmentally-friendly production technologies. I develop a model with differentiated products and imperfectly-informed consumers. Consumers care about the environmental characteristics of goods (for example, how they were produced), but cannot directly observe these product characteristics. Firms differ in their abilities to develop "clean" technologies, but have no ince...

  8. Use of 3-[18F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

    Directory of Open Access Journals (Sweden)

    Reik Löser

    2013-05-01

    Full Text Available 3-[18F]Fluoropropanesulfonyl chloride, a recently proposed prosthetic agent for fluorine-18 labelling, was prepared in a two-step radiosynthesis via 3-[18F]fluoropropyl thiocyanate as an intermediate. Two benzenesulfonate-based radiolabelling precursors were prepared by various routes. Comparing the reactivities of 3-thiocyanatopropyl nosylate and the corresponding tosylate towards [18F]fluoride the former proved to be superior accounting for labelling yields of up to 85%. Conditions for a reliable transformation of 3-[18F]fluoropropyl thiocyanate to the corresponding sulfonyl chloride with the potential for automation have been identified. The reaction of 3-[18F]fluoropropanesulfonyl chloride with eight different aliphatic and aromatic amines was investigated and the identity of the resulting 18F-labelled sulfonamides was confirmed chromatographically by comparison with their nonradioactive counterparts. Even for weakly nucleophilic amines such as 4-nitroaniline the desired radiolabelled sulfonamides were accessible in satisfactory yields owing to systematic variation of the reaction conditions. With respect to the application of the 18F-fluoropropansulfonyl group to the labelling of compounds relevant as imaging agents for positron emission tomography (PET, the stability of N-(4-fluorophenyl-3-fluoropropanesulfonamide against degradation catalysed by carboxylesterase was investigated and compared to that of the analogous fluoroacetamide.

  9. A systematic investigation of differential effects of cell culture substrates on the extent of artifacts in single-molecule tracking.

    Directory of Open Access Journals (Sweden)

    Laura C Zanetti-Domingues

    Full Text Available Single-molecule techniques are being increasingly applied to biomedical investigation, notwithstanding the numerous challenges they pose in terms of signal-to-noise ratio issues. Non-specific binding of probes to glass substrates, in particular, can produce experimental artifacts due to spurious molecules on glass, which can be particularly deleterious in live-cell tracking experiments. In order to resolve the issue of non-specific probe binding to substrates, we performed systematic testing of a range of available surface coatings, using three different proteins, and then extended our assessment to the ability of these coatings to foster cell growth and retain non-adhesive properties. Linear PEG, a passivating agent commonly used both in immobilized-molecule single-molecule techniques and in tissue engineering, is able to both successfully repel non-specific adhesion of fluorescent probes and to foster cell growth when functionalized with appropriate adhesive peptides. Linear PEG treatment results in a significant reduction of tracking artifacts in EGFR tracking with Affibody ligands on a cell line expressing EGFR-eGFP. The findings reported herein could be beneficial to a large number of experimental situations where single-molecule or single-particle precision is required.

  10. Enumerating molecules.

    Energy Technology Data Exchange (ETDEWEB)

    Visco, Donald Patrick, Jr. (, . Tennessee Technological University, Cookeville, TN); Faulon, Jean-Loup Michel; Roe, Diana C.

    2004-04-01

    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

  11. Labelling and biological evaluation of therapeutic radiopharmaceuticals

    International Nuclear Information System (INIS)

    The paper describes research aimed at developing radiolabelled agents using 'bone seeking' molecules and peptides as the target specific moieties. For the study of bone seeking molecules, hydroxyethylene diphosphonate (HEDP) and dimercaptosuccinic acid (DMSA) (V) were labelled with 188Re. For peptide radiolabelling, 99mTc and 111In were used as the diagnostic radioisotopes, and 90Y was used as the therapeutic radioisotope. The labelling yielded agents with high radiochemical purity. The labelled compounds - 188Re- HEDP, 188Re-DMSA(V), 111In-DOTATOC, 99mTc-HYNIC-TATE, 90Y-DOTATOC and 90Y-DOTATATE - were evaluated in mice, rats and healthy beagle dogs. All compounds were also tested in dogs with spontaneous tumours as pathological models. Biodistribution studies showed that the molecules accumulated in their respective target cells. Spontaneous tumours in dogs offered a unique opportunity to investigate the diagnostic utility and therapeutic behaviour of the radiopharmaceuticals. (author)

  12. Fluorescent labels and their use in separations

    Science.gov (United States)

    Mathies, Richard A.; Glazer, Alexander; Ju, Jingyue

    1997-01-01

    Compositions are provided comprising sets of fluorescent labels carrying pairs of donor and acceptor dye molecules, designed for efficient excitation of the donors at a single wavelength and emission from the acceptor in each of the pairs at different wavelengths. The different molecules having different donor-acceptor pairs can be modified to have substantially the same mobility under separation conditions, by varying the distance between the donor and acceptor in a given pair. Particularly, the fluorescent compositions find use as labels in sequencing nucleic acids.

  13. Issues in Data Labelling

    NARCIS (Netherlands)

    Cowie, Roddy; Cox, Cate; Martin, Jeam-Claude; Batliner, Anton; Heylen, Dirk; Karpouzis, Kostas; Cowie, Roddy; Pelachaud, Catherine; Petta, Paolo

    2011-01-01

    Labelling emotion databases is not a purely technical matter. It is bound up with theoretical issues. Different issues affect labelling of emotional content, labelling of the signs that convey emotion, and labelling of the relevant context. Linked to these are representational issues, involving time

  14. 99mTc: Labeling Chemistry and Labeled Compounds

    Science.gov (United States)

    Alberto, R.; Abram, U.

    This chapter reviews the radiopharmaceutical chemistry of technetium related to the synthesis of perfusion agents and to the labeling of receptor-binding biomolecules. To understand the limitations of technetium chemistry imposed by future application of the complexes in nuclear medicine, an introductory section analyzes the compulsory requirements to be considered when facing the incentive of introducing a novel radiopharmaceutical into the market. Requirements from chemistry, routine application, and market are discussed. In a subsequent section, commercially available 99mTc-based radiopharmaceuticals are treated. It covers the complexes in use for imaging the most important target organs such as heart, brain, or kidney. The commercially available radiopharmaceuticals fulfill the requirements outlined earlier and are discussed with this background. In a following section, the properties and perspectives of the different generations of radiopharmaceuticals are described in a general way, covering characteristics for perfusion agents and for receptor-specific molecules. Technetium chemistry for the synthesis of perfusion agents and the different labeling approaches for target-specific biomolecules are summarized. The review comprises a general introduction to the common approaches currently in use, employing the N x S4-x , [3+1] and 2-hydrazino-nicotinicacid (HYNIC) method as well as more recent strategies such as the carbonyl and the TcN approach. Direct labeling without the need of a bifunctional chelator is briefly reviewed as well. More particularly, recent developments in the labeling of concrete targeting molecules, the second generation of radiopharmaceuticals, is then discussed and prominent examples with antibodies/peptides, neuroreceptor targeting small molecules, myocardial imaging agents, vitamins, thymidine, and complexes relevant to multidrug resistance are given. In addition, a new approach toward peptide drug development is described. The section

  15. Succesful labelling schemes

    DEFF Research Database (Denmark)

    Juhl, Hans Jørn; Stacey, Julia

    2001-01-01

    It is usual practice to evaluate the success of a labelling scheme by looking at the awareness percentage, but in many cases this is not sufficient. The awareness percentage gives no indication of which of the consumer segments that are aware of and use labelling schemes and which do not. In the...... spring of 2001 MAPP carried out an extensive consumer study with special emphasis on the Nordic environmentally friendly label 'the swan'. The purpose was to find out how much consumers actually know and use various labelling schemes. 869 households were contacted and asked to fill in a questionnaire....... 664 households returned a completed questionnaire. There were five answering categories for each label in the questionnaire: * have not seen the label before. * I have seen the label before but I do not know the precise contents of the labelling scheme. * I have seen the label before, I do not know...

  16. Synthesizing labeled compounds

    International Nuclear Information System (INIS)

    A metabolic study is presented of the chemical reactions provided by isotopic labeling and NMR spectroscopy. Synthesis of 13C-labeled D-glucose, a 6-carbon sugar, involves adding a labeled nitrile group to the 5-carbon sugar D-arabinose by reaction with labeled hydrogen cyanide. The product of this reaction is then reduced and hydrolyzed to a mixture of the labeled sugars. The two sugars are separated by absorption chromotography. The synthesis of 13C-labeled L-tyrosine, an amino acid, is also presented

  17. Fluorescent Labeling of Plasmid DNA and mRNA: Gains and Losses of Current Labeling Strategies.

    Science.gov (United States)

    Rombouts, K; Braeckmans, K; Remaut, K

    2016-02-17

    Live-cell imaging has provided the life sciences with insights into the cell biology and dynamics. Fluorescent labeling of target molecules proves to be indispensable in this regard. In this Review, we focus on the current fluorescent labeling strategies for nucleic acids, and in particular mRNA (mRNA) and plasmid DNA (pDNA), which are of interest to a broad range of scientific fields. By giving a background of the available techniques and an evaluation of the pros and cons, we try to supply scientists with all the information needed to come to an informed choice of nucleic acid labeling strategy aimed at their particular needs. PMID:26670733

  18. Mental Labels and Tattoos

    Science.gov (United States)

    Hyatt, I. Ralph

    1977-01-01

    Discusses the ease with which mental labels become imprinted in our system, six basic axioms for maintaining negative mental tattoos, and psychological processes for eliminating mental tattoos and labels. (RK)

  19. Pesticide Product Label System

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Pesticide Product Label System (PPLS) provides a collection of pesticide product labels (Adobe PDF format) that have been approved by EPA under Section 3 of the...

  20. On Online Labeling with Polynomially Many Labels

    DEFF Research Database (Denmark)

    Babka, Martin; Bulánek, Jan; Cunat, Vladimír; Koucky, Michal; Saks, Michael

    2012-01-01

    In the online labeling problem with parameters n and m we are presented with a sequence of nkeys from a totally ordered universe U and must assign each arriving key a label from the label set {1,2,…,m} so that the order of labels (strictly) respects the ordering on U. As new keys arrive it may be...... necessary to change the labels of some items; such changes may be done at any time at unit cost for each change. The goal is to minimize the total cost. An alternative formulation of this problem is the file maintenance problem, in which the items, instead of being labeled, are maintained in sorted order in...... are known that use O(n logn) relabelings. A matching lower bound was claimed in [7]. That proof involved two distinct steps: a lower bound for a problem they call prefix bucketing and a reduction from prefix bucketing to online labeling. The reduction seems to be incorrect, leaving a (seemingly...

  1. Group specific internal standard technology (GSIST) for simultaneous identification and quantification of small molecules

    Science.gov (United States)

    Adamec, Jiri; Yang, Wen-Chu; Regnier, Fred E

    2014-01-14

    Reagents and methods are provided that permit simultaneous analysis of multiple diverse small molecule analytes present in a complex mixture. Samples are labeled with chemically identical but isotopically distince forms of the labeling reagent, and analyzed using mass spectrometry. A single reagent simultaneously derivatizes multiple small molecule analytes having different reactive functional groups.

  2. Gold Nanoparticle Labels Amplify Ellipsometric Signals

    Science.gov (United States)

    Venkatasubbarao, Srivatsa

    2008-01-01

    The ellipsometric method reported in the immediately preceding article was developed in conjunction with a method of using gold nanoparticles as labels on biomolecules that one seeks to detect. The purpose of the labeling is to exploit the optical properties of the gold nanoparticles in order to amplify the measurable ellipsometric effects and thereby to enable ultrasensitive detection of the labeled biomolecules without need to develop more-complex ellipsometric instrumentation. The colorimetric, polarization, light-scattering, and other optical properties of nanoparticles depend on their sizes and shapes. In the present method, these size-and-shape-dependent properties are used to magnify the polarization of scattered light and the diattenuation and retardance of signals derived from ellipsometry. The size-and-shape-dependent optical properties of the nanoparticles make it possible to interrogate the nanoparticles by use of light of various wavelengths, as appropriate, to optimally detect particles of a specific type at high sensitivity. Hence, by incorporating gold nanoparticles bound to biomolecules as primary or secondary labels, the performance of ellipsometry as a means of detecting the biomolecules can be improved. The use of gold nanoparticles as labels in ellipsometry has been found to afford sensitivity that equals or exceeds the sensitivity achieved by use of fluorescence-based methods. Potential applications for ellipsometric detection of gold nanoparticle-labeled biomolecules include monitoring molecules of interest in biological samples, in-vitro diagnostics, process monitoring, general environmental monitoring, and detection of biohazards.

  3. Fluorescent RNA labeling using self-alkylating ribozymes.

    Science.gov (United States)

    Sharma, Ashwani K; Plant, Joshua J; Rangel, Alexandra E; Meek, Kirsten N; Anamisis, April J; Hollien, Julie; Heemstra, Jennifer M

    2014-08-15

    The ability to fluorescently label specific RNA sequences is of significant utility for both in vitro and live cell applications. Currently, most RNA labeling methods utilize RNA-nucleic acid or RNA-protein molecular recognition. However, in the search for improved RNA labeling methods, harnessing the small-molecule recognition capabilities of RNA is rapidly emerging as a promising alternative. Along these lines, we propose a novel strategy in which a ribozyme acts to promote self-alkylation with a fluorophore, providing a robust, covalent linkage between the RNA and the fluorophore. Here we describe the selection and characterization of ribozymes that promote self-labeling with fluorescein iodoacetamide (FIA). Kinetic studies reveal a second-order rate constant that is on par with those of other reactions used for biomolecular labeling. Additionally, we demonstrate that labeling is specific to the ribozyme sequences, as FIA does not react nonspecifically with RNA. PMID:24896502

  4. Deuterium labeled cannabinoids

    International Nuclear Information System (INIS)

    Complex reactions involving ring opening, ring closure and rearrangements hamper complete understanding of the fragmentation processes in the mass spectrometric fragmentation patterns of cannabinoids. Specifically labelled compounds are very powerful tools for obtaining more insight into fragmentation mechanisms and ion structures and therefore the synthesis of specifically deuterated cannabinoids was undertaken. For this, it was necessary to investigate the preparation of cannabinoids, appropriately functionalized for specific introduction of deuterium atom labels. The results of mass spectrometry with these labelled cannabinoids are described. (Auth.)

  5. Labelling Fashion Markets

    OpenAIRE

    Aspers, P.

    2008-01-01

    The present article discusses how an ethical and environmental labelling system can be implemented in fashion garment markets. Consumers act in markets that provide them with more information than their limited cognitive capacity allows them to handle. Ethical and environmental labelling in markets characterized by change, such as the fashion garment market, makes decision-making even more complicated. The ethical and environmental labelling system proposed here is designed to alleviate firms...

  6. Blood cell labelling

    International Nuclear Information System (INIS)

    The labelling of blood cells in vitro for subsequent in vivo studies was one of the earliest applications of radioactive tracers in clinical medicine and laid the foundations for many important contributions to the advancement of knowledge of human blood cell pathophysiology. The characteristics required for satisfactory clinical studies, the mechanisms of cell labelling, the problems of radiation or chemical damage to the labelled cells and some examples of modern clinical applications are described and discussed. (Author)

  7. Labelling of live cells using fluorescent aptamers: binding reversal with DNA nucleases

    OpenAIRE

    Terazono Hideyuki; Anzai Yu; Soloviev Mikhail; Yasuda Kenji

    2010-01-01

    Abstract A reversible cell labelling method has been developed for non-destructive and non-invasive cell labelling and purification. Our method uses high affinity single strand DNA (ssDNA) aptamers against surface exposed target molecules on cells. The aptamers are subsequently removed from the cell surface using DNase nuclease treatment. We exemplified our method by labelling human acute lymphoblastic leukemia cells with Qdot-ssDNA aptamers, and restoring them to the label-free condition by ...

  8. On labelled compounds nomenclature

    International Nuclear Information System (INIS)

    Different approaches of major labelled compounds producers to their nomenclature in technical and commercial documentation are discussed. Some draft options of a standard technical guide document for labelled compounds nomenclature rules are suggested. Such a document after due discussion by the experts will serve to unification of the labelled compounds nomenclature within the frame of the CMEA member-countries co-operation in this field. The suggested options are based on the general recommendations by the International Union of Pure and Applied Chemistry and incorporate some more accurate definitions originating from the labelled compounds production and application experience

  9. Bone marrow origin of Ia molecules purified from epidermal cells

    International Nuclear Information System (INIS)

    Using radiation bone marrow chimeras, we have shown that Ia molecules purified from epidermal cell preparations of the mouse reflect the Ia phenotype of the bone marrow donor. This result strongly suggests that Ia molecules are synthesized by a bone-marrow-derived cell in the epidermis. Furthermore, results of peptide map analysis of immunoprecipitated biosynthetically labeled Ia suggest that the Ia molecules found in skin are identical to those found on B lymphocytes. These results support biochemical as well as serologic identity

  10. Single Molecule Raman Detection of Enkephalin on Silver Colloidal Particles

    DEFF Research Database (Denmark)

    Kneipp, Katrin; Kneipp, Holger; Abdali, Salim; Berg, Rolf W.; Bohr, Henrik

    2004-01-01

    Raman signal the enkephalin molecules have been attached to silver colloidal cluster structures. The experiments demonstrate that the SERS signal of the strongly enhanced ring breathing vibration of phenylalanine at 1000 cm-1 can be used as “intrinsic marker” for detecting a single enkephalin molecule...... and for monitoring its diffusion on the surface of the silver colloidal cluster without using a specific label molecule....

  11. Tomography of epidermal growth factor receptor binding to fluorescent Affibody in vivo studied with magnetic resonance guided fluorescence recovery in varying orthotopic glioma sizes

    Science.gov (United States)

    Holt, Robert W.; Demers, Jennifer-Lynn H.; Sexton, Kristian J.; Gunn, Jason R.; Davis, Scott C.; Samkoe, Kimberley S.; Pogue, Brian W.

    2015-02-01

    The ability to image targeted tracer binding to epidermal growth factor receptor (EGFR) was studied in vivo in orthotopically grown glioma tumors of different sizes. The binding potential was quantified using a dual-tracer approach, which employs a fluorescently labeled peptide targeted to EGFR and a reference tracer with similar pharmacokinetic properties but no specific binding, to estimate the relative bound fraction from kinetic compartment modeling. The recovered values of binding potential did not vary significantly as a function of tumor size (1 to 33 mm3), suggesting that binding potential may be consistent in the U251 tumors regardless of size or stage after implantation. However, the fluorescence yield of the targeted fluorescent tracers in the tumor was affected significantly by tumor size, suggesting that dual-tracer imaging helps account for variations in absolute uptake, which plague single-tracer imaging techniques. Ex vivo analysis showed relatively high spatial heterogeneity in each tumor that cannot be resolved by tomographic techniques. Nonetheless, the dual-tracer tomographic technique is a powerful tool for longitudinal bulk estimation of receptor binding.

  12. Stable isotopes labelled compounds

    International Nuclear Information System (INIS)

    The catalogue on stable isotopes labelled compounds offers deuterium, nitrogen-15, and multiply labelled compounds. It includes: (1) conditions of sale and delivery, (2) the application of stable isotopes, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  13. Labeling and Delinquency.

    Science.gov (United States)

    Adams, Mike S.; Robertson, Craig T.; Gray-Ray, Phyllis; Ray, Melvin C.

    2003-01-01

    Index comprised of six contrasting descriptive adjectives was used to measure incarcerated youths' perceived negative labeling from the perspective of parents, teachers, and peers. Results provided partial support for hypothesis that juveniles who choose a greater number of negative labels will report more frequent delinquent involvement. Labeling…

  14. Comparative study of fixation of Co57 labelled bleomycin, labelled gallium citrate and Hg197 labelled mercury chloride, benign or malignant pulmonary lesions

    International Nuclear Information System (INIS)

    Over the last ten years, numerous labelled molecules have been used in lung diseases, in order to attempt definite localisation of primary or secondary carcinoma. Three of these substances are now used: cobalt 57-labelled bleomycin, Hg197Cl2 and Ga67 citrate. A study of 34 patient with malignant or tuberculous lung disease with definite diagnosis, permitted demonstration of the fact that the highest uptake, or the best images, were obtained with labelled bleomycin. However, the long period of Co57 limits its indications in young subjects and, in these cases, HgCl2 is indicated

  15. Label Fusion Strategy Selection

    Directory of Open Access Journals (Sweden)

    Nicolas Robitaille

    2012-01-01

    Full Text Available Label fusion is used in medical image segmentation to combine several different labels of the same entity into a single discrete label, potentially more accurate, with respect to the exact, sought segmentation, than the best input element. Using simulated data, we compared three existing label fusion techniques—STAPLE, Voting, and Shape-Based Averaging (SBA—and observed that none could be considered superior depending on the dissimilarity between the input elements. We thus developed an empirical, hybrid technique called SVS, which selects the most appropriate technique to apply based on this dissimilarity. We evaluated the label fusion strategies on two- and three-dimensional simulated data and showed that SVS is superior to any of the three existing methods examined. On real data, we used SVS to perform fusions of 10 segmentations of the hippocampus and amygdala in 78 subjects from the ICBM dataset. SVS selected SBA in almost all cases, which was the most appropriate method overall.

  16. OR Specimen Labeling.

    Science.gov (United States)

    Zervakis Brent, Mary Ann

    2016-02-01

    Mislabeled surgical specimens jeopardize patient safety and quality care. The purpose of this project was to determine whether labeling surgical specimens with two patient identifiers would result in an 80% reduction in specimen labeling errors within six months and a 100% reduction in errors within 12 months. Our failure mode effects analysis found that the lack of two patient identifiers per label was the most unsafe step in our specimen handling process. We piloted and implemented a new process in the OR using the Plan-Do-Check-Act conceptual framework. The audit process included collecting data and making direct observations to determine the sustainability of the process change; however, the leadership team halted the direct observation audit after four months. The total number of surgical specimen labeling errors was reduced by only 60% within six months and 62% within 12 months; therefore, the goal of the project was not met. However, OR specimen labeling errors were reduced. PMID:26849982

  17. Nutrition Facts: Reading the Label

    Science.gov (United States)

    ... My Go4Life Get Free Stuff Be a Partner Nutrition Facts: Reading the Label Reading labels can help ... of information on their labels or packaging about nutrition and food safety. Product dates . You might see ...

  18. Radioactive labelled orgotein

    International Nuclear Information System (INIS)

    The preparation and use of radioactively labelled orgotein, i.e. water-soluble protein congeners in pure, injectable form, is described. This radiopharmaceutical is useful in scintigraphy, especially for visualization of the kidneys where the orgotein is rapidly concentrated. Details of the processes for labelling bovine orgotein with sup(99m)Tc, 60Co, 125I or 131I are specified. The pharmaceutical preparation of the labelled orgotein for intravenous and parenteral administration is also described. Examples using either sup(99m)TC or 125I-orgotein in scintiscanning dogs' kidneys are given. (UK)

  19. Photoactivatable protein labeling by singlet oxygen mediated reactions.

    Science.gov (United States)

    To, Tsz-Leung; Medzihradszky, Katalin F; Burlingame, Alma L; DeGrado, William F; Jo, Hyunil; Shu, Xiaokun

    2016-07-15

    Protein-protein interactions regulate many biological processes. Identification of interacting proteins is thus an important step toward molecular understanding of cell signaling. The aim of this study was to investigate the use of photo-generated singlet oxygen and a small molecule for proximity labeling of interacting proteins in cellular environment. The protein of interest (POI) was fused with a small singlet oxygen photosensitizer (miniSOG), which generates singlet oxygen ((1)O2) upon irradiation. The locally generated singlet oxygen then activated a biotin-conjugated thiol molecule to form a covalent bond with the proteins nearby. The labeled proteins can then be separated and subsequently identified by mass spectrometry. To demonstrate the applicability of this labeling technology, we fused the miniSOG to Skp2, an F-box protein of the SCF ubiquitin ligase, and expressed the fusion protein in mammalian cells and identified that the surface cysteine of its interacting partner Skp1 was labeled by the biotin-thiol molecule. This photoactivatable protein labeling method may find important applications including identification of weak and transient protein-protein interactions in the native cellular context, as well as spatial and temporal control of protein labeling. PMID:27220724

  20. Clinical applications of cells labelling

    International Nuclear Information System (INIS)

    Blood cells labelled with radionuclides are reviewed and main applications are described. Red blood cell labelling by both random and specific principle. A table with most important clinical uses, 99mTc labelling of RBC are described pre tinning and in vivo reduction of Tc, in vitro labelling and administration of labelled RBC and in vivo modified technique. Labelled leucocytes with several 99mTc-complex radiopharmaceuticals by in vitro technique and specific monoclonal s for white cells(neutrofiles). Labelled platelets for clinical use and research by in vitro technique and in vivo labelling

  1. Radioiodine labelling of insulin using dimethylsulfoxide as a labelling-aid

    International Nuclear Information System (INIS)

    Using dimethylsulfoxide (DMSO) as a labelling aid, insulin 126I of radioimmunoassay use has been effectively prepared. A small amount of DMSO was added to usual labelling mixture and the reaction time was controlled. The labelled insulin obtained in such a way showed improved bindabilities to the antibody and thus expressed larger dose-gradients in the plots of standard dose-response curves even though the labelling rate was decreased to some extent. However, by extending the reaction time to about 1 min, average labelling yield of 30% could be obtained. The average increase of bindability (B/F) in definite antiserum dilution was 2.5 comparing with 1.5 obtained in the absence of DMSO. Thus, the net bindability increase was 70% of those obtained in the absence of DMSO. By means of NMR spectrometry, it has been confirmed that the DMSO in the labelling mixture is converted to dimethylsulfone by chloramine-T. The results, generally agreed with the Stagg's postulation, were discussed in view of a competitive oxidation of DMSO with disulfide linkages of the insulin molecule by the chloramine-T. (author)

  2. FDA Online Label Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The drug labels and other drug-specific information on this Web site represent the most recent drug listing information companies have submitted to the Food and...

  3. Like your labels?

    Science.gov (United States)

    Field, Michele

    2010-01-01

    The descriptive “conventions” used on food labels are always evolving. Today, however, the changes are so complicated (partly driven by legislation requiring disclosures about environmental impacts, health issues, and geographical provenance) that these labels more often baffle buyers than enlighten them. In a light-handed manner, the article points to how sometimes reading label language can be like deciphering runes—and how if we are familiar with the technical terms, we can find a literal meaning, but still not see the implications. The article could be ten times longer because food labels vary according to cultures—but all food-exporting cultures now take advantage of our short attention-span when faced with these texts. The question is whether less is more—and if so, in this contest for our attention, what “contestant” is voted off. PMID:21539053

  4. Stereoselective synthesis of stable-isotope-labeled amino acids

    Energy Technology Data Exchange (ETDEWEB)

    Unkefer, C.J.; Martinez, R.A.; Silks, L.A. III [Los Alamos National Laboratory, NM (United States); Lodwig, S.N. [Centralia College, WA (United States)

    1994-12-01

    For magnetic resonance and vibrational spectroscopies to reach their full potential, they must be used in combination with sophisticated site-specific stable isotope labeling of biological macromolecules. Labeled amino acids are required for the study of the structure and function of enzymes and proteins. Because there are 20 common amino acids, each with its own distinguishing chemistry, they remain a synthetic challenge. The Oppolzer chiral auxiliary provides a general tool with which to approach the synthesis of labeled amino acids. By using the Oppolzer auxiliary, amino acids can be constructed from several small molecules, which is ideal for stable isotope labeling. In addition to directing the stereochemistry at the {alpha}-carbon, the camphorsultam can be used for stereo-specific isotope labeling at prochiral centers in amino acids. By using the camphorsultam auxiliary we have the potential to synthesize virtually any isotopomer of all of the common amino acids.

  5. Certified Rule Labeling

    OpenAIRE

    Nagele, Julian; Zankl, Harald

    2015-01-01

    The rule labeling heuristic aims to establish confluence of (left-)linear term rewrite systems via decreasing diagrams. We present a formalization of a confluence criterion based on the interplay of relative termination and the rule labeling in the theorem prover Isabelle. Moreover, we report on the integration of this result into the certifier CeTA, facilitating the checking of confluence certificates based on decreasing diagrams for the first time. The power of the method is illustrated by ...

  6. Labelling of Vincamine derivatives

    International Nuclear Information System (INIS)

    Tritium labelled Vincamine and ethyl apovincaminate (Cavinton) have been prepared on the bases of known stereospecific synthesis. High specific activity compounds were obtained by the catalytic tritiation of appropriate unsaturated starting compounds. When the structure of the unsaturated starting compounds was changed (even rather for from the reaction centre) instead of the catalytic addition of tritium a specific hydrogen-tritium exchange reaction was found to be the main labelling process

  7. Labelling of electricity

    International Nuclear Information System (INIS)

    This comprehensive report for the Swiss Federal Office of Energy (SFOE) presents a possible course of action to be taken to provide a means of declaring the sources of electrical power, as is foreseen in the draft of new Swiss electricity market legislation. The report presents the basic ideas behind the idea and defines the terms used such as labelling, certificates and declarations. Also, the legal situation in the European Union and in Switzerland is examined and a quantitative overview of electricity production and consumption is presented. Suggestions for a labelling scheme are made and some of the problems to be expected are looked at. The report also presents a series of examples of labelling schemes already implemented in other countries, such as Austria, Great Britain, Sweden and Germany. Tradable certificates and tracking systems are discussed as are initial quality labels like the Swiss 'Naturemade' label for green power. A concrete recommendation for the declaration and labelling of electricity in Switzerland is presented and various factors to be considered such as import/export, pumped storage, distribution losses, small-scale producers as well as the time-scales for introduction are discussed

  8. A comparison of two 99Tcm leucocyte labelling techniques

    International Nuclear Information System (INIS)

    Full text: 111In-oxine labelled leucocytes are routinely used for the diagnosis of various inflammatory conditions. The search for a good 99Tcm labelling agent continues in order to prevent the radio-toxicity effects to lymphocytes caused by the high radiation dose from 111In decay. 99Tcm-HMPAO, a lipophilic, neutral molecule, has a leucocyte labelling mechanism similar to that of 111In-oxine (Passive Diffusion).Granulocytes are preferentially labelled with 99Tcm-HMPAO. Another method for labelling leucocytes with 99Tcm has been achieved with the polycationic, hydrophilic molecule, Modified Poly-lysine (MPL). Most mammalian cells have negatively charged surfaces which electrostatically attract cationic 99Tcm-MPL. Surface adsorption followed by internalisation by endocytosis leads to cell labelling. The entire mechanism is termed non-specific adsorptive endocytosis. The aim of this study was to compare the in vitro stability of the 99Tcm-leucocyte label prepared with 99Tcm-MPL to that prepared with 99Tcm-HMPAO. Leucocytes were isolated from venous blood using the 2% methyl cellulose sedimentation method. Half of the leucocytes were incubated in 99Tcm-HMPAO (1.5 GBq, 1 mL) for 15 minutes, the remaining leucocytes were incubated in 99Tcm- MPL (1.5 GBq, 1 mL) for 45 minutes. The labelling stability of the leucocytes was determined by incubation at room temperature in serum for 120 minutes. 99Tcm-MPL labels all components of the leucocyte population equally well and its improved labelling efficiency and stability may have application in studying the trafficking of T-lymphocytes in adoptive immunotherapy. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  9. Streaming Label Learning for Modeling Labels on the Fly

    OpenAIRE

    You, Shan; Xu, Chang; Wang, Yunhe; Xu, Chao; Tao, Dacheng

    2016-01-01

    It is challenging to handle a large volume of labels in multi-label learning. However, existing approaches explicitly or implicitly assume that all the labels in the learning process are given, which could be easily violated in changing environments. In this paper, we define and study streaming label learning (SLL), i.e., labels are arrived on the fly, to model newly arrived labels with the help of the knowledge learned from past labels. The core of SLL is to explore and exploit the relations...

  10. Eco-labelling, competition and environment: Endogenization of labelling criteria

    OpenAIRE

    Ben Youssef, Adel; Lahmandi-Ayed, Rim

    2008-01-01

    This paper suggests a modelling of the labelling procedure consistent with empirical observations, that allows the endogenous calculation of labelling criteria. The authority in charge of the labelling program chooses the level of labelling criteria so as to maximise the social surplus, anticipating competition between firms in environmental qualities and prices. While accounting simply for the informational role of labels, this model allows to understand observed behavior such as firms' igno...

  11. A simple synthesis of [sup 13]C[sub 6]-labelled flavone and 5-methoxyflavone

    Energy Technology Data Exchange (ETDEWEB)

    Ares, J.J.; Wehmeyer, K.R. (Procter and Gamble Co., Cincinnati, OH (United States))

    1994-07-01

    The [sup 13]C[sub 6]-labelled molecules, flavone and 5-methoxyflavone, with the carbon-13 label at all six carbons of the aromatic B ring, have been prepared for use as internal standards in isotope dilution-mass spectrometry. The key step involves addition of a labelled benzoyl group to the methyl group of a hydroxyacetophenone, forming a 1,3-diketone. Overall yields from [sup 13]C[sub 6]-benzoic acid were 38% for the labelled flavone and 45% for the labelled 5-methoxyflavone. (Author).

  12. On online labeling with polynomially many labels

    Czech Academy of Sciences Publication Activity Database

    Babka, M.; Bulánek, Jan; Čunát, V.; Koucký, Michal; Saks, M.

    Berlin : Springer, 2012 - (Epstein, L.; Ferragina, P.), s. 121-132 ISBN 978-3-642-33089-6. - (Lecture Notes in Computer Science. 7501). [20th Annual European Symposium on Algorithms (ESA 2012). Ljubljana (SI), 10.09.2012-12.09.2012] R&D Projects: GA ČR GAP202/10/0854; GA AV ČR IAA100190902 Institutional support: RVO:67985840 Keywords : online labeling * file maintenance problem * lower bounds Subject RIV: BA - General Mathematics http://link.springer.com/chapter/10.1007/978-3-642-33090-2_12

  13. European consumers and nutrition labelling

    DEFF Research Database (Denmark)

    Wills, Josephine M.; Grunert, Klaus G.; Celemín, Laura Fernández;

    2009-01-01

    Nutrition labelling of food in Europe is not compulsory, unless a nutrition or health claim is made for the product. The European Commission is proposing mandatory nutrition labelling, even front of pack labelling with nutrition information. Yet, how widespread is nutrition labelling in the EU...

  14. Genetic algorithms for map labeling

    NARCIS (Netherlands)

    Dijk, Steven Ferdinand van

    2002-01-01

    Map labeling is the cartographic problem of placing the names of features (for example cities or rivers) on the map. A good labeling has no intersections between labels. Even basic versions of the problem are NP-hard. In addition, realistic map-labeling problems deal with many cartographic constr

  15. Off-Label Drug Use

    Science.gov (United States)

    ... Your Local Offices Close + - Text Size Off-label Drug Use What is off-label drug use? In the United States new drugs are ... unapproved use of a drug. Is off-label drug use legal? The off-label use of FDA- ...

  16. Radio labeling with preassigned frequencies.

    OpenAIRE

    2004-01-01

    A radio labeling of a graph G is an assignment of pairwise distinct, positive integer labels to the vertices of G such that labels of adjacent vertices differ by at least $2$. The radio labeling problem (RL) consists in determining a radio labeling that minimizes the maximum label that is used (the so-called span of the labeling). RL is a well-studied problem, mainly motivated by frequency assignment problems in which transmitters are not allowed to operate on the same frequency channel. We c...

  17. CD molecules 2005: human cell differentiation molecules

    Czech Academy of Sciences Publication Activity Database

    Zola, H.; Swart, B.; Nicholson, I.; Aasted, B.; Bensussan, A.; Boumsell, L.; Buckley, C.; Clark, G.; Drbal, Karel; Engel, P.; Hart, D.; Hořejší, Václav; Isacke, C.; Macardle, P.; Malavasi, F.; Mason, D.; Olive, D.; Saalmüller, A.; Schlossman, S.F.; Schwartz-Albiez, R.; Simmons, P.; Tedder, T.F.; Uguccioni, M.; Warren, H.

    2005-01-01

    Roč. 106, č. 9 (2005), s. 3123-3126. ISSN 0006-4971 Institutional research plan: CEZ:AV0Z5052915 Keywords : CD molecules * leukocyte antigen Subject RIV: EC - Immunology Impact factor: 10.131, year: 2005

  18. Radioactive labelling of peptidic hormones

    International Nuclear Information System (INIS)

    The labelling of peptidic hormones requires stability, specificity and sensitivity of the label. Introduction of a radioactive atome is one way to satisfy these criteria. Several processes have been described to prepare radioactive TRF: synthesis of the peptide with labelled aminoacids or introduction of the label into the hormone. In that approach, tritium can be substituted in the imidazole ring, via precursors activating the proper carbon. Monoiodo TRF leads essentially to tritium labelling of the 5 positions whereas monoazo TRF allows the preparation of 3H TRF labelled in the 2 positions. Di-substituted TRF leads to labelling into the 2 and 5 carbons. Labelled analogs of TRF can be prepared with labelled iodine; further developments of peptide labelling, will be presented. In particular, the homolytic scission of the C-iodine, bond by photochemical activation. The nascent carbon radical can be stabilized by a tritiated scavenger. This approach eliminates the use of heavy metal catalysts

  19. Single Molecule Fluorescence Measurements of Ribosomal Translocation Dynamics

    OpenAIRE

    Chen, Chunlai; Stevens, Benjamin; Kaur, Jaskarin; Cabral, Diana; Liu, Hanqing; Wang, Yuhong; Zhang, Haibo; Rosenblum, Gabriel; Smilansky, Zeev; Goldman, Yale E.; Cooperman, Barry S.

    2011-01-01

    We employ single-molecule fluorescence resonance energy transfer (smFRET) to study structural dynamics over the first two elongation cycles of protein synthesis, using ribosomes containing either Cy3-labeled ribosomal protein L11 and A- or P-site Cy5-labeled tRNA or Cy3 and Cy5 labeled tRNAs. Pre-translocation (PRE) complexes demonstrate fluctuations between classical and hybrid forms, with concerted motions of tRNAs away from L11 and from each other when classical complex converts to hybrid ...

  20. Synthesis of labeled compounds

    International Nuclear Information System (INIS)

    Intermediate compounds labeled with 13C included methane, sodium cyanide, methanol, ethanol, and acetonitrile. A new method for synthesizing 15N-labeled 4-ethylsulfonyl-1-naphthalene-sulfonamide was developed. Studies were conducted on pathways to oleic-1-13C acid and a second pathway investigated was based on carbonation of 8-heptadecynylmagnesium bromide with CO2 to prepare sterolic acid. Biosynthetic preparations included glucose-13C from starch isolated from tobacco leaves following photosynthetic incubation with 13CO2 and galactose-13C from galactosylglycerol-13C from kelp. Research on growth of organisms emphasized photosynthetic growth of algae in which all cellular carbon is labeled. Preliminary experiments were performed to optimize the growth of Escherichia coli on sodium acetate-13C

  1. Fluorine-18 labelled compounds

    International Nuclear Information System (INIS)

    The work presented in this thesis deals with the problems involved in the adaption of reactor-produced fluorine-18 to the synthesis of 18F-labelled organic fluorine compounds. Several 18F-labelling reagents were prepared and successfully applied. The limitations to the synthetic possibilities of reactor-produced fluoride-18 become manifest in the last part of the thesis. An application to the synthesis of labelled aliphatic fluoro amino acids has appeared to be unsuccessful as yet, although some other synthetic approaches can be indicated. Seven journal articles (for which see the availability note) are used to compose the four chapters and three appendices. The connecting text gives a survey of known 18F-compounds and methods for preparing such compounds. (Auth.)

  2. Semantic Role Labeling

    CERN Document Server

    Palmer, Martha; Xue, Nianwen

    2011-01-01

    This book is aimed at providing an overview of several aspects of semantic role labeling. Chapter 1 begins with linguistic background on the definition of semantic roles and the controversies surrounding them. Chapter 2 describes how the theories have led to structured lexicons such as FrameNet, VerbNet and the PropBank Frame Files that in turn provide the basis for large scale semantic annotation of corpora. This data has facilitated the development of automatic semantic role labeling systems based on supervised machine learning techniques. Chapter 3 presents the general principles of applyin

  3. Chemiluminescent Labeled Organic Reagents and Their Use in Analysis of Organic Compounds

    OpenAIRE

    Hummelen, Jan C.; Wynberg, Hans

    1990-01-01

    Thermochemically induced luminescence is generated in a fluorescent labeled organic compound containing a covalently bonded fluorescent label which is a polycyclic aromatic radical having at least three linearly fused benzene rings and capable of being excited to a fluorescent electronic excited state by energy transfer from an energy donor molecule or radical having an electronic excited state, by a process comprising generating an energy donor radical or molecule by a thermochemical reactio...

  4. Design and synthesis of tracers labelled with a short-lived positron emitting

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) is currently used widely as a non-invasive tool for dynamic studies of regional in vivo biochemistry in biomedical research as well as in medical diagnosis. Its advance has increased the demand for labeled tracers and stimulated the search for synthetic strategies for rapid synthesis of tracer molecules labeled with short-lived radionuclides. The paper deals with various topics in this field with emphasis on the design and the synthesis of interesting radiolabeled tracer molecules. It first discusses requirements for the design of labeled tracer molecules. Important factors in selecting an appropriate tracer molecule for PET study include the type of radionuclide to be used, position for labeling, and appropriate stereochemical configuration. The report then discusses position specific labeling for studies of metabolism, kinetic isotopic effects in PET, multiple isotopic labeling for non-invasive validation of metabolism, synthetic strategies for labeling tracer molecules with short-lived radionuclides, and creation of chirality by asymmetric organic and enzyme catalyzed synthesis. (N.K.)

  5. Formation of Ultracold Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Cote, Robin [Univ. of Connecticut, Storrs, CT (United States)

    2016-01-28

    Advances in our ability to slow down and cool atoms and molecules to ultracold temperatures have paved the way to a revolution in basic research on molecules. Ultracold molecules are sensitive of very weak interactions, even when separated by large distances, which allow studies of the effect of those interactions on the behavior of molecules. In this program, we have explored ways to form ultracold molecules starting from pairs of atoms that have already reached the ultracold regime. We devised methods that enhance the efficiency of ultracold molecule production, for example by tuning external magnetic fields and using appropriate laser excitations. We also investigates the properties of those ultracold molecules, especially their de-excitation into stable molecules. We studied the possibility of creating new classes of ultra-long range molecules, named macrodimers, thousand times more extended than regular molecules. Again, such objects are possible because ultra low temperatures prevent their breakup by collision. Finally, we carried out calculations on how chemical reactions are affected and modified at ultracold temperatures. Normally, reactions become less effective as the temperature decreases, but at ultracold temperatures, they can become very effective. We studied this counter-intuitive behavior for benchmark chemical reactions involving molecular hydrogen.

  6. Labeling of herbicide femesafen

    International Nuclear Information System (INIS)

    5-[2-chroo-4-(trifluoromethyl ) phenoxy]-N-(methyl sulphonyl )-2-niorobenzamide [femesafen] was labeled by six steps. Radio-chemical yield was 19.15%. TLC analysis of the final product showed that the radiochemical purity is not less than 99%. (authors)

  7. Waisda?: video labeling game

    NARCIS (Netherlands)

    Hildebrand, M.; Brinkerink, M.; Gligorov, R.; Steenbergen, M. van; Huijkman, J.; Oomen, J.

    2013-01-01

    The Waisda? video labeling game is a crowsourcing tool to collect user-generated metadata for video clips. It follows the paradigm of games-with-a-purpose, where two or more users play against each other by entering tags that describe the content of the video. Players score points by entering the sa

  8. Understanding Food Labels

    Science.gov (United States)

    ... girls Eating healthy at restaurants Special food issues Vegetarian eating Eating for strong bones Quiz: Food Facts Links to more information girlshealth glossary girlshealth.gov home http://www.girlshealth.gov/ Home Nutrition Healthy eating for girls Understanding food labels Understanding ...

  9. Stabilization of labelled compounds

    International Nuclear Information System (INIS)

    This invention concerns a composition including a labelled compound, and the vitamin B 12. This vitamin gives a red colour to the solution and stabilize it radiochemically, allowing to transport the solution at ambient temperature and a storage at 4 degrees celsius. (N.C.). 5 refs

  10. Genetic algorithms for map labeling

    OpenAIRE

    Dijk, Steven Ferdinand van

    2002-01-01

    Map labeling is the cartographic problem of placing the names of features (for example cities or rivers) on the map. A good labeling has no intersections between labels. Even basic versions of the problem are NP-hard. In addition, realistic map-labeling problems deal with many cartographic constraints, which pose more demands on how the labels should be placed in relation to their surroundings. For example, a label is preferably placed above and to the right of a city. These two aspects (comb...

  11. Trapping molecules on chips

    CERN Document Server

    Santambrogio, Gabriele

    2015-01-01

    In the last years, it was demonstrated that neutral molecules can be loaded on a microchip directly from a supersonic beam. The molecules are confined in microscopic traps that can be moved smoothly over the surface of the chip. Once the molecules are trapped, they can be decelerated to a standstill, for instance, or pumped into selected quantum states by laser light or microwaves. Molecules are detected on the chip by time-resolved spatial imaging, which allows for the study of the distribution in the phase space of the molecular ensemble.

  12. Light-up properties of complexes between thiazole orange-small molecule conjugates and aptamers

    OpenAIRE

    Pei, Renjun; Rothman, Jeffrey; Xie, Yuli; Stojanovic, Milan N.

    2009-01-01

    The full understanding of dynamics of cellular processes hinges on the development of efficient and non-invasive labels for intracellular RNA species. Light-up aptamers binding fluorogenic ligands show promise as specific labels for RNA species containing those aptamers. Herein, we took advantage of existing, non-light-up aptamers against small molecules and demonstrated a new class of light-up probes in vitro. We synthesized two conjugates of thiazole orange dye to small molecules (GMP and A...

  13. Spin labels. Applications in biology

    International Nuclear Information System (INIS)

    The main applications of spin labels in the study of biomembranes, enzymes, nucleic acids, in pharmacology, spin immunoassay are reviewed along with the fundamentals of the spin label method. 137 references. (author)

  14. Use the Nutrition Facts Label

    Science.gov (United States)

    ... Features Spokespeople News Archive eNewsletters Calendar Use the Nutrition Facts Label You can help your family eat ... to some of their favorite foods. Use the Nutrition Facts label found on food packages to make ...

  15. Labeling lake water with tritium

    Science.gov (United States)

    Frederick, B.J.

    1963-01-01

    A method of packaging tritiated water in a manner that facilitates safe handling in environmental labeling operations, and procedures followed in labeling a large body of water with a small volume of tritiated water are described. ?? 1963.

  16. Physics of Polymers under Nanoscopic Confinement: a Single Molecule Study

    NARCIS (Netherlands)

    Keshavarz, M.

    2016-01-01

    Physicist Masoumeh Keshavarz studied the thermal motion of a fluorescently labelled, individual “reporter” polymer molecule, surrounded and entangled by a gel of similar but unlabelled polymers. Owing to their extreme length and stiffness, it is possible to follow the shape and the motion of the rep

  17. Food Labels Tell the Story!

    Science.gov (United States)

    ... My World From the Label to the Table! Food Labels Tell the Story! What is in food? Food provides your body with all of the ... your food choices. Nutrition Facts—the Labels on Food Products Beginning in 1994, the US government began ...

  18. Isotopically labelled benzodiazepines

    International Nuclear Information System (INIS)

    This paper reports on the benzodiazepines which are a class of therapeutic agents. Improvements in the analytical methodology in the areas of biochemistry and pharmacology were significant, particularly in the application of chromatographic and spectroscopic techniques. In addition, the discovery and subsequent development of tritium and carbon-14 as an analytical tool in the biological sciences were essentially post-world war II phenomena. Thus, as these new chemical entities were found to be biologically active, they could be prepared in labeled form for metabolic study, biological half-life determination (pharmacokinetics), tissue distribution study, etc. This use of tracer methodology has been liberally applied to the benzodiazepines and also more recently to the study of receptor-ligand interactions, in which tritium, carbon-11 or fluorine-18 isotopes have been used. The history of benzodiazepines as medicinal agents is indeed an interesting one; an integral part of that history is their use in just about every conceivable labeled form

  19. Nomenclature for labelled compounds

    International Nuclear Information System (INIS)

    This paper report on isotopically labelled compounds. The first indexing system for isotopically labelled organic compounds is generally credited to Boughton and named after him. An extension of his principles for designating compounds containing hydrogen isotopes has been part of the Chemical Abstracts Service index nomenclature system for many years. After close on five years labor the IUPAC sponsored Commission on Nomenclature of Organic Chemistry presented in 1979 their findings on Isotopically Modified Compounds. The system codified in their rules provides for recognition of various types of isotopic modification and is therefore of more general applicability. Concurrently the rules for the nomenclature of isotopically modified inorganic compounds are developed. These are to be seen as supplementing and extending the guidelines laid down in the IUPAC Inorganic Nomenclature Rules already published

  20. Labelling, Deviance and Media

    OpenAIRE

    Greer, C.

    2014-01-01

    Labelling theory is a perspective that emerged as a distinctive approach to criminology during the 1960s, and was a major seedbed of the radical and critical perspectives that became prominent in the 1970s. It represented the highpoint of an epistemological shift within the social sciences away from positivism – which had dominated criminological enquiry since the late-1800s – and toward an altogether more relativistic stance on the categories and concepts of crime and control. It inspired a ...

  1. Eco-labelling

    OpenAIRE

    Kuna-Marszałek, Anetta

    2016-01-01

    Considering environmental protection requirements in business operations may, in the long run, determine if a lasting comparative advantage can be achieved. That is why our textbook, rich in case studies, identifies not only the threats a business may pose to the environment but stresses the ways of reducing its negative impact. It discusses, among other things, the concept of corporate social responsibility, environmental management systems, methods and the importance of eco-labelling goods ...

  2. Myocardial arterial spin labeling

    OpenAIRE

    Kober, Frank; Jao, Terrence; Troalen, Thomas; Nayak, Krishna S.

    2016-01-01

    Arterial spin labeling (ASL) is a cardiovascular magnetic resonance (CMR) technique for mapping regional myocardial blood flow. It does not require any contrast agents, is compatible with stress testing, and can be performed repeatedly or even continuously. ASL-CMR has been performed with great success in small-animals, but sensitivity to date has been poor in large animals and humans and remains an active area of research. This review paper summarizes the development of ASL-CMR techniques, c...

  3. Optical detection of single non-absorbing molecules using the surface plasmon of a gold nanorod

    CERN Document Server

    Zijlstra, Peter; Orrit, Michel

    2012-01-01

    Current optical detection schemes for single molecules require light absorption, either to produce fluorescence or direct absorption signals. This severely limits the range of molecules that can be detected, because most molecules are purely refractive. Metal nanoparticles or dielectric resonators detect non-absorbing molecules by a resonance shift in response to a local perturbation of the refractive index, but neither has reached single-protein sensitivity. The most sensitive plasmon sensors to date detect single molecules only when the plasmon shift is amplified by a highly polarizable label or by a localized precipitation reaction on the particle's surface. Without amplification, the sensitivity only allows for the statistical detection of single molecules. Here we demonstrate plasmonic detection of single molecules in realtime, without the need for labeling or amplification. We monitor the plasmon resonance of a single gold nanorod with a sensitive photothermal assay and achieve a ~ 700-fold increase in ...

  4. Stearic acid spin labels in lipid bilayers: insight through atomistic simulations.

    Science.gov (United States)

    Stimson, Lorna; Dong, Lei; Karttunen, Mikko; Wisniewska, Anna; Dutka, Małgorzata; Róg, Tomasz

    2007-11-01

    Spin-labeled stearic acid species are commonly used for electron paramagnetic resonance (EPR) studies of cell membranes to investigate phase transitions, fluidity, and other physical properties. In this paper, we use large-scale molecular dynamics simulations to investigate the position and behavior of nitroxide spin labels attached to stearic acid molecules in dipalmitoylphosphatidylcholine (DPPC) bilayers. The results of these studies are potentially very important for the interpretation of EPR spectra, which rely on assumptions about the position of the label in the membrane. Additionally, we investigate the effect of chirality and ionization of the carboxyl group of the label. For a non-ionized species, we observe that spin-label molecules are even able to make flip-flop transitions between the leaflets of the bilayer. Such transitions have been previously observed only in very rare cases in molecular simulations. PMID:17929861

  5. Linerless label device and method

    KAUST Repository

    Binladen, Abdulkari

    2016-01-14

    This apparatus and method for applying a linerless label to an end user product includes a device with a printer for printing on a face surface of a linerless label, and a release coat applicator for applying a release coat to the face surface of the label; another device including an unwinder unit (103) to unwind a roll of printed linerless label; a belt (108); a glue applicator (102) for applying glue to the belt; a nip roller (106) for contacting and applying pressure to the face surface of the linerless label such that the glue on the belt transfers to the back surface of the linerless label; at least one slitting knife 105) positioned downstream the belt and a rewinder unit (104) positioned downstream the slitting knife; and a third device which die cuts and applies the linerless label to an end user object.

  6. Label-Guided Graph Exploration with Adjustable Ratio of Labels

    CERN Document Server

    Zhang, Meng; Tang, Jijun

    2012-01-01

    The graph exploration problem is to visit all the nodes of a connected graph by a mobile entity, e.g., a robot. The robot has no a priori knowledge of the topology of the graph or of its size. Cohen et al. \\cite{Ilcinkas08} introduced label guided graph exploration which allows the system designer to add short labels to the graph nodes in a preprocessing stage; these labels can guide the robot in the exploration of the graph. In this paper, we address the problem of adjustable 1-bit label guided graph exploration. We focus on the labeling schemes that not only enable a robot to explore the graph but also allow the system designer to adjust the ratio of the number of different labels. This flexibility is necessary when maintaining different labels may have different costs or when the ratio is pre-specified. We present 1-bit labeling (two colors, namely black and white) schemes for this problem along with a labeling algorithm for generating the required labels. Given an $n$-node graph and a rational number $\\rh...

  7. Single Molecule DNA Detection with an Atomic Vapor Notch Filter

    CERN Document Server

    Uhland, Denis; Widmann, Matthias; Lee, Sang-Yun; Wrachtrup, Jörg; Gerhardt, Ilja

    2015-01-01

    The detection of single molecules has facilitated many advances in life- and material-sciences. Commonly, it founds on the fluorescence detection of single molecules, which are for example attached to the structures under study. For fluorescence microscopy and sensing the crucial parameters are the collection and detection efficiency, such that photons can be discriminated with low background from a labeled sample. Here we show a scheme for filtering the excitation light in the optical detection of single stranded labeled DNA molecules. We use the narrow-band filtering properties of a hot atomic vapor to filter the excitation light from the emitted fluorescence of a single emitter. The choice of atomic sodium allows for the use of fluorescent dyes, which are common in life-science. This scheme enables efficient photon detection, and a statistical analysis proves an enhancement of the optical signal of more than 15% in a confocal and in a wide-field configuration.

  8. Electron correlation in molecules

    CERN Document Server

    Wilson, S

    2007-01-01

    Electron correlation effects are of vital significance to the calculation of potential energy curves and surfaces, the study of molecular excitation processes, and in the theory of electron-molecule scattering. This text describes methods for addressing one of theoretical chemistry's central problems, the study of electron correlation effects in molecules.Although the energy associated with electron correlation is a small fraction of the total energy of an atom or molecule, it is of the same order of magnitude as most energies of chemical interest. If the solution of quantum mechanical equatio

  9. Artifacts in single-molecule localization microscopy.

    Science.gov (United States)

    Burgert, Anne; Letschert, Sebastian; Doose, Sören; Sauer, Markus

    2015-08-01

    Single-molecule localization microscopy provides subdiffraction resolution images with virtually molecular resolution. Through the availability of commercial instruments and open-source reconstruction software, achieving super resolution is now public domain. However, despite its conceptual simplicity, localization microscopy remains prone to user errors. Using direct stochastic optical reconstruction microscopy, we investigate the impact of irradiation intensity, label density and photoswitching behavior on the distribution of membrane proteins in reconstructed super-resolution images. We demonstrate that high emitter densities in combination with inappropriate photoswitching rates give rise to the appearance of artificial membrane clusters. Especially, two-dimensional imaging of intrinsically three-dimensional membrane structures like microvilli, filopodia, overlapping membranes and vesicles with high local emitter densities is prone to generate artifacts. To judge the quality and reliability of super-resolution images, the single-molecule movies recorded to reconstruct the images have to be carefully investigated especially when investigating membrane organization and cluster analysis. PMID:26138928

  10. Labeling of virus components for advanced, quantitative imaging analyses.

    Science.gov (United States)

    Sakin, Volkan; Paci, Giulia; Lemke, Edward A; Müller, Barbara

    2016-07-01

    In recent years, investigation of virus-cell interactions has moved from ensemble measurements to imaging analyses at the single-particle level. Advanced fluorescence microscopy techniques provide single-molecule sensitivity and subdiffraction spatial resolution, allowing observation of subviral details and individual replication events to obtain detailed quantitative information. To exploit the full potential of these techniques, virologists need to employ novel labeling strategies, taking into account specific constraints imposed by viruses, as well as unique requirements of microscopic methods. Here, we compare strengths and limitations of various labeling methods, exemplify virological questions that were successfully addressed, and discuss challenges and future potential of novel approaches in virus imaging. PMID:26987299

  11. Labelled compounds. (Pt. B)

    International Nuclear Information System (INIS)

    Since the end of World War II there has been a tremendous increase in the number of compounds that have been synthesized with radioactive or stable isotopes. They have found application in many diverse fields, so much so, that hardly a single area in pure and applied science has not benefited. Not surprisingly it has been reflected in appearance of related publications. The early proceedings of the Symposia on Advances in Trace Methodology were soon followed by various Euratom sponsored meetings in which methods of preparing and storing labelled compounds featured prominently. In due course a resurgence of interest in stable isotopes, brought about by their greater availability (also lower cost) and partly by development of new techniques such as gas chromatography - mass spectrometry (gc-ms), led to the publication of proceedings of several successful conferences. More recently conferences dealing with the synthesis and applications of isotopes and isotopically labelled compounds have been established on a regular basis. In addition to the proceedings of conferences and journal publications individuals left their mark by producing definitive texts, usually on specific nuclides. Only the classic two volume publication of Murray and Williams (Organic syntheses with isotopes, New York 1985), now over 30 years old and out of print, attempted to do justice to several nuclides. With the large amount of work that has been undertaken since then it seems unlikely that an updated edition could be produced. The alternative strategy was to ask scientists currently active to review specific areas and this is the approach adopted in the present series of monographs. In this way it is intended to cover the broad advances that have been made in the synthesis and applications of isotopes and isotopically labelled compounds in the physical and biomedical sciences. (author). refs.; figs.; tabs

  12. Trace fluorescent labeling for protein crystallization

    Energy Technology Data Exchange (ETDEWEB)

    Pusey, Marc, E-mail: marc.pusey@ixpressgenes.com; Barcena, Jorge; Morris, Michelle; Singhal, Anuj; Yuan, Qunying; Ng, Joseph [iXpressGenes Inc., 601 Genome Way, Huntsville, AL 35810 (United States)

    2015-06-27

    The presence of a covalently bound fluorescent probe at a concentration of <0.5% does not affect the outcome of macromolecule crystallization screening experiments. Additionally, the fluorescence can be used to determine new, not immediately apparent, lead crystallization conditions. Fluorescence can be a powerful tool to aid in the crystallization of proteins. In the trace-labeling approach, the protein is covalently derivatized with a high-quantum-yield visible-wavelength fluorescent probe. The final probe concentration typically labels ≤0.20% of the protein molecules, which has been shown to not affect the crystal nucleation or diffraction quality. The labeled protein is then used in a plate-screening experiment in the usual manner. As the most densely packed state of the protein is the crystalline form, then crystals show as the brightest objects in the well under fluorescent illumination. A study has been carried out on the effects of trace fluorescent labeling on the screening results obtained compared with nonlabeled protein, and it was found that considering the stochastic nature of the crystal nucleation process the presence of the probe did not affect the outcomes obtained. Other effects are realised when using fluorescence. Crystals are clearly seen even when buried in precipitate. This approach also finds ‘hidden’ leads, in the form of bright spots, with ∼30% of the leads found being optimized to crystals in a single-pass optimization trial. The use of visible fluorescence also enables the selection of colors that bypass interfering substances, and the screening materials do not have to be UV-transparent.

  13. Waisda?: video labeling game

    OpenAIRE

    Hildebrand, Michiel; Brinkerink, M.; Gligorov, R.; Steenbergen, Van; Huijkman, J.; Oomen, J.

    2013-01-01

    The Waisda? video labeling game is a crowsourcing tool to collect user-generated metadata for video clips. It follows the paradigm of games-with-a-purpose, where two or more users play against each other by entering tags that describe the content of the video. Players score points by entering the same tags as one of the other players. As a result each video that is played in the game is annotated with tags that are anchored to a time point in the video. Waisda? has been deployed in two projec...

  14. From Label to Practice

    DEFF Research Database (Denmark)

    Byrkjeflot, Haldor; Strandgaard, Jesper; Svejenova, Silviya

    2013-01-01

    This article examines the process of creation of new Nordic cuisine (NNC) as a culinary innovation, focusing on the main stages, actors, and mechanisms that shaped the new label and its practices and facilitated its diffusion in the region and internationally. Fast-paced diffusion was possible...... because NNC was conceived as an identity movement, triggered by active involvement of entrepreneurial leaders from the culinary profession, high-profile political supporters, legitimating scientists, disseminating media, and interpreting audiences. It was facilitated by three mechanisms: First, the use of...

  15. Labeled bile acids

    International Nuclear Information System (INIS)

    A general short procedure for the introduction of 13C to the side chain of bile acids is described. Suitable (Z)-pregn-17(20)-enes are key intermediates, while the isotope is introduced by an ene reaction with [1,2,3-13C3]-methyl propiolate. For the labeling with tritium, the unlabeled product of the ene synthesis, a Δsup(5,16,22)-triene was saturated selectively at 16,17 and 22,23 with tritium gas. (author)

  16. A Food Labeling

    Science.gov (United States)

    ... " ﻗﺎﻧﻮن اﻟﺒﻄﺎﻗﺎت واﻟﺘﻮﻋﻴﺔ اﻟﻐﺬاﺋﻴﺔ " [ Nutrition Labeling and Education Act ... ﻟﻠﻌﺼﻴﺮ اﻟﻤﻜﻮن ﺑﺈﺿﺎﻓﺔ اﻟﻤﺎء إﻟﻰ ﺧﻼﺻﺔ ﻣﺮآﺰة : ﻳﺠﺮى اﻟﺤﺴﺎب ﻣﻦ ﺟﺪول Brix ﻓﻲ 21 CFR 101.30(h)(1) ...

  17. Towards Multi Label Text Classification through Label Propagation

    Directory of Open Access Journals (Sweden)

    Shweta C. Dharmadhikari

    2012-06-01

    Full Text Available Classifying text data has been an active area of research for a long time. Text document is multifaceted object and often inherently ambiguous by nature. Multi-label learning deals with such ambiguous object. Classification of such ambiguous text objects often makes task of classifier difficult while assigning relevant classes to input document. Traditional single label and multi class text classification paradigms cannot efficiently classify such multifaceted text corpus. Through our paper we are proposing a novel label propagation approach based on semi supervised learning for Multi Label Text Classification. Our proposed approach models the relationship between class labels and also effectively represents input text documents. We are using semi supervised learning technique for effective utilization of labeled and unlabeled data for classification. Our proposed approach promises better classification accuracy and handling of complexity and elaborated on the basis of standard datasets such as Enron, Slashdot and Bibtex.

  18. Electron-molecule collisions

    CERN Document Server

    Takayanagi, Kazuo

    1984-01-01

    Scattering phenomena play an important role in modern physics. Many significant discoveries have been made through collision experiments. Amongst diverse kinds of collision systems, this book sheds light on the collision of an electron with a molecule. The electron-molecule collision provides a basic scattering problem. It is scattering by a nonspherical, multicentered composite particle with its centers having degrees of freedom of motion. The molecule can even disintegrate, Le., dissociate or ionize into fragments, some or all of which may also be molecules. Although it is a difficult problem, the recent theoretical, experimental, and computational progress has been so significant as to warrant publication of a book that specializes in this field. The progress owes partly to technical develop­ ments in measurements and computations. No less important has been the great and continuing stimulus from such fields of application as astrophysics, the physics of the earth's upper atmosphere, laser physics, radiat...

  19. Single molecules and nanotechnology

    CERN Document Server

    Vogel, Horst

    2007-01-01

    This book focuses on recent advances in the rapidly evolving field of single molecule research. These advances are of importance for the investigation of biopolymers and cellular biochemical reactions, and are essential to the development of quantitative biology. Written by leading experts in the field, the articles cover a broad range of topics, including: quantum photonics of organic dyes and inorganic nanoparticles their use in detecting properties of single molecules the monitoring of single molecule (enzymatic) reactions single protein (un)folding in nanometer-sized confined volumes the dynamics of molecular interactions in biological cells The book is written for advanced students and scientists who wish to survey the concepts, techniques and results of single molecule research and assess them for their own scientific activities.

  20. CNN: Single-label to Multi-label

    OpenAIRE

    Wei, Yunchao; Xia, Wei; Huang, Junshi; Ni, Bingbing; Dong, Jian; Zhao, Yao; Yan, Shuicheng

    2014-01-01

    Convolutional Neural Network (CNN) has demonstrated promising performance in single-label image classification tasks. However, how CNN best copes with multi-label images still remains an open problem, mainly due to the complex underlying object layouts and insufficient multi-label training images. In this work, we propose a flexible deep CNN infrastructure, called Hypotheses-CNN-Pooling (HCP), where an arbitrary number of object segment hypotheses are taken as the inputs, then a shared CNN is...

  1. Optothermal Molecule Trap

    OpenAIRE

    Duhr, Stefan; Braun, Dieter

    2006-01-01

    Thermophoresis moves molecules along temperature gradients, typically from hot to cold. We superpose fluid flow with thermophoretic molecule flow under well defined microfluidic conditions, imaged by fluorescence microscopy. DNA is trapped and accumulated 16-fold in regions where both flows move in opposite directions. Strong 800-fold accumulation is expected, however with slow trapping kinetics. The experiment is equally described by a three-dimensional and one-dimensional analytical model. ...

  2. Modeling the effects of labeling

    DEFF Research Database (Denmark)

    Juhl, Hans Jørn; Fjord, Thomas Ahle; Poulsen, Carsten Stig

    A new approach to evaluate the consequences of labeling is presented and applied to test the potential effect of a label on fresh fish. Labeling effects on quality perceptions and overall quality are studied. The empirical study is based on an experimental design and nearly 500 respondents partic...... participated in an in home test. The results indicate that catch time alone is not enough to work as an efficient predictor of actual perceived quality.......A new approach to evaluate the consequences of labeling is presented and applied to test the potential effect of a label on fresh fish. Labeling effects on quality perceptions and overall quality are studied. The empirical study is based on an experimental design and nearly 500 respondents...

  3. Edge colouring by total labellings

    DEFF Research Database (Denmark)

    Brandt, Stephan; Rautenbach, D.; Stiebitz, M.;

    2010-01-01

    We introduce the concept of an edge-colouring total k-labelling. This is a labelling of the vertices and the edges of a graph G with labels 1, 2, ..., k such that the weights of the edges define a proper edge colouring of G. Here the weight of an edge is the sum of its label and the labels of its...... two endvertices. We define χ (G) to be the smallest integer k for which G has an edge-colouring total k-labelling. This parameter has natural upper and lower bounds in terms of the maximum degree Δ of G : ⌈ (Δ + 1) / 2 ⌉ ≤ χ (G) ≤ Δ + 1. We improve the upper bound by 1 for every graph and prove χ (G...

  4. Visualization of DNA molecules in time during electrophoresis

    Science.gov (United States)

    Lubega, Seth

    1991-01-01

    For several years individual DNA molecules have been observed and photographed during agarose gel electrophoresis. The DNA molecule is clearly the largest molecule known. Nevertheless, the largest molecule is still too small to be seen using a microscope. A technique developed by Morikawa and Yanagida has made it possible to visualize individual DNA molecules. When these long molecules are labeled with appropriate fluorescence dyes and observed under a fluorescence microscope, although it is not possible to directly visualize the local ultrastructure of the molecules, yet because they are long light emitting chains, their microscopic dynamical behavior can be observed. This visualization works in the same principle that enables one to observe a star through a telescope because it emits light against a dark background. The dynamics of individual DNA molecules migrating through agarose matrix during electrophoresis have been described by Smith et al. (1989), Schwartz and Koval (1989), and Bustamante et al. (1990). DNA molecules during agarose gel electrophoresis advance lengthwise thorough the gel in an extended configuration. They display an extension-contraction motion and tend to bunch up in their leading ends as the 'heads' find new pores through the gel. From time to time they get hooked on obstacles in the gel to form U-shaped configurations before they resume their linear configuration.

  5. Synthesis and properties of differently charged chemiluminescent acridinium ester labels.

    Science.gov (United States)

    Natrajan, Anand; Sharpe, David

    2013-02-14

    Chemiluminescent acridinium dimethylphenyl esters containing N-sulfopropyl groups in the acridinium ring are highly sensitive, hydrophilic labels that are used in automated immunoassays for clinical diagnostics. Light emission from these labels is triggered with alkaline peroxide in the presence of a cationic surfactant. At physiological pH, N-sulfopropyl acridinium esters exist as water adducts that are commonly referred to as pseudobases. Pseudobase formation, which results from addition of water to the zwitterionic N-sulfopropyl acridinium ring, neutralizes the positive charge on the acridinium nitrogen and imparts a net negative charge to the label due to the sulfonate moiety. As a consequence, N-sulfopropyl acridinium ester conjugates of small molecule haptens as well as large molecules such as proteins gain negative charges at neutral pH. In the current study, we describe the synthesis and properties of two new hydrophilic acridinium dimethylphenyl ester labels where the net charge in the labels was altered. In one label, the structure of the hydrophilic N-alkyl group attached to the acridinium ring was changed so that the pseudobase of the label contains no net charge. In the second acridinium ester, two additional negative charges in the form of sulfopropyl groups were added to the acridinium ring to make this label's pseudobase strongly anionic. Chemiluminescence measurements of these labels, as well as their conjugates of an antibody with a neutral pI, indicate that acridinium ester charge while having a modest effect on emission kinetics has little influence on light output. However, our results demonstrate that acridinium ester charge can affect protein pI, apparent chemiluminescence stability and non-specific binding of protein conjugates to microparticles. These results emphasize the need for careful consideration of acridinium ester charge in order to optimize reagent stability and performance in immunoassays. In the current study, we observed that

  6. HaloTag protein-mediated specific labeling of living cells with quantum dots

    International Nuclear Information System (INIS)

    Quantum dots emerge as an attractive alternative to small molecule fluorophores as fluorescent tags for in vivo cell labeling and imaging. This communication presents a method for specific labeling of live cells using quantum dots. The labeling is mediated by HaloTag protein expressed at the cell surface which forms a stable covalent adduct with its ligand (HaloTag ligand). The labeling can be performed in one single step with quantum dot conjugates that are functionalized with HaloTag ligand, or in two steps with biotinylated HaloTag ligand first and followed by streptavidin coated quantum dots. Live cell fluorescence imaging indicates that the labeling is specific and takes place at the cell surface. This HaloTag protein-mediated cell labeling method should facilitate the application of quantum dots for live cell imaging

  7. Limitations of Label-Free Sensors in Serum Based Molecular Diagnostics

    CERN Document Server

    Varma, Manoj M

    2015-01-01

    Immunoassay formats applicable for clinical or point-of-care diagnostics fall into two broad classes. One which uses labeled secondary antibodies for signal transduction and the other which does not require the use of any labels. Comparison of the limits of detection (LoD) reported by these two sensing approaches over a wide range of detection techniques and target molecules in serum revealed that labeled techniques achieve 2-3 orders of magnitude better LoDs. Further, a vast majority of commercial tests and recent examples of technology translations are based on labeled assay formats. In light of this data, it is argued that extension of traditional labeled approaches and enhancing their functionality may have better clinical impact than the development of newer label-free techniques.

  8. Aggregating Labels in Crowdsourcing Data

    OpenAIRE

    Priisalu, Maria; Grey, Francois; Segal, Ben

    2015-01-01

    Project Specification Crowdsourcing is gaining popularity in academia with the launch of crowdsourcing platforms such as Crowdcrafting [Lombraña, 2015] and GeoTagX [UNOSAT, 2015]. There have been a number of proposed algorithms for the aggregation of true labels and a confusion matrix from crowdsourced labels for ordinal, nominal and binary labels. The work here consists of an implementation of the Dawid Skene [Dawid 1979] adaptation of the Expectation Maximization algorithm [D...

  9. Classification and Labelling for Biocides

    OpenAIRE

    Rubbiani, Maristella

    2015-01-01

    CLP and biocides The EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures, the CLP-Regulation, entered into force on 20th January, 2009. Since 1st December, 2010 the classification, labelling and packaging of substances has to comply with this Regulation. For mixtures, the rules of this Regulation are mandatory from 1st June, 2015; this means that until this date classification, labelling and packaging could either be carried out according to D...

  10. Co-Labeling for Multi-View Weakly Labeled Learning.

    Science.gov (United States)

    Xu, Xinxing; Li, Wen; Xu, Dong; Tsang, Ivor W

    2016-06-01

    It is often expensive and time consuming to collect labeled training samples in many real-world applications. To reduce human effort on annotating training samples, many machine learning techniques (e.g., semi-supervised learning (SSL), multi-instance learning (MIL), etc.) have been studied to exploit weakly labeled training samples. Meanwhile, when the training data is represented with multiple types of features, many multi-view learning methods have shown that classifiers trained on different views can help each other to better utilize the unlabeled training samples for the SSL task. In this paper, we study a new learning problem called multi-view weakly labeled learning, in which we aim to develop a unified approach to learn robust classifiers by effectively utilizing different types of weakly labeled multi-view data from a broad range of tasks including SSL, MIL and relative outlier detection (ROD). We propose an effective approach called co-labeling to solve the multi-view weakly labeled learning problem. Specifically, we model the learning problem on each view as a weakly labeled learning problem, which aims to learn an optimal classifier from a set of pseudo-label vectors generated by using the classifiers trained from other views. Unlike traditional co-training approaches using a single pseudo-label vector for training each classifier, our co-labeling approach explores different strategies to utilize the predictions from different views, biases and iterations for generating the pseudo-label vectors, making our approach more robust for real-world applications. Moreover, to further improve the weakly labeled learning on each view, we also exploit the inherent group structure in the pseudo-label vectors generated from different strategies, which leads to a new multi-layer multiple kernel learning problem. Promising results for text-based image retrieval on the NUS-WIDE dataset as well as news classification and text categorization on several real-world multi

  11. The radioactive labeling of monocytes

    International Nuclear Information System (INIS)

    With the aim of studying a possible relationship between circulating monocytes and Sternberg-Reed cells investigations were started on the specific labeling of monocytes. In this thesis the literature on the pertinent data has been reviewed and a series of experiments on the monocyte labeling procedure has been described. The principles of cell labeling with radioactive compounds were discussed. 1. Total separation of the particular cell population to be labeled and subsequent labeling with a non-specific radiopharmaceutical. 2. Specific cell labeling in a mixture of cell types based on a well defined affinity of the cell under study for the radiopharmaceutical used. Next the radionuclides that can be used for cell labeling purposes were discussed with special attention for 111In and its chelates. The principles of radiodosimetry were also discussed shortly. This section was focussed on the radiation dose the labeled cells receive because of the intracellular localized radioactivity. The radiation burden is high in comparison to amounts of radiation known to affect cell viability. A newly developed method for labeling monocytes specifically by phagocytosis of 111In-Fe-colloid without apparent loss of cells was described in detail. (Auth.)

  12. The stereoconfiguration of newly formed molecules of bis(monoacylglycero)phosphate in BHK cells.

    Science.gov (United States)

    Joutti, A

    1979-10-26

    Newly formed molecules of bis(monoacylglycero)phosphate (known also as lysobisphosphatidic acid), which were labeled with 32Pi in cultured BHK cells during relatively short pulses, were subjected to stereoanalysis. In contrast to the high proportion of sn-1-glycerophosphate residues in the bulk of the bis(monoacylglycero)phosphate molecules, the newly formed molecules were rich in sn-3-glycerophosphate residues. PMID:508774

  13. 76 FR 75809 - Prior Label Approval System: Generic Label Approval

    Science.gov (United States)

    2011-12-05

    ... the type of packaging material on which the label is printed; n. Brand name changes, provided that... poultry products will take effect January 1, 2012 (75 FR 82148, Dec. 29, 2010). These mandatory features..., location, and indication of final color. To obtain sketch label approval, domestic meat and...

  14. Laser labeling, a safe technology to label produce

    Science.gov (United States)

    Laser labeling of fruits and vegetables is an alternative means to label produce. Low energy CO2 laser beams etch the surface showing the contrasting underlying layer. These etched surfaces can promote water loss and potentially allow for entry of decay organisms. The long-term effects of laser labe...

  15. Interaction between a "processed" ovalbumin peptide and Ia molecules

    DEFF Research Database (Denmark)

    Buus, S; Colon, S; Smith, C;

    1986-01-01

    The binding of 125I-labeled immunogenic peptides to purified Ia molecules in detergent solution was examined by equilibrium dialysis. We used the chicken ovalbumin peptide ovalbumin-(323-339)-Tyr, which is immunogenic in the BALB/c mouse and restricted to I-Ad. 125I-labeled ovalbumin-(323-339)-Tyr...... I-Ak but not to I-Ek, I-Ad, or I-Ed. Thus, a specific interaction between Ia and antigen that correlates with the major histocompatibility complex restriction was demonstrated, strongly arguing in favor of a determinant selection hypothesis for such restriction....

  16. Synthesis of tritium-labeled vitamin A and its analogs

    International Nuclear Information System (INIS)

    Metabolic and pharmacologic studies of Vitamin A and its analogs related to the prevention of lung cancer and other epithelial cancers required tritium-labeled Vitamin A analogs and β-carotene at high specific activity. Syntheses of some of the isomers were therefore developed in the laboratory, as described in the paper. The advantages of the scheme shown are that : 1. Tritiums are introduced into the molecule by catalytic hydrogenation, thus affording high specific activity. 2. It uses an allylic rearrangement of tritiated vinyl-β-ionol to C15-phosphonium salt, which is condensed with C5-nitrile to give C20-skeleton of retinonitrile. 3. It permits the development of milder methods to convert tritium-labeled retinaldehyde, as a common intermediate, to the other retinoids (i.e., retinoic acid, retinol, and retinyl acetate). Furthermore, tritium-labeled all-trans-β-carotene, an important carotenoid, has been obtained from the retinaldehyde

  17. Radio-labelled humic materials in migration studies

    International Nuclear Information System (INIS)

    Humic- and fulvic acids are able to complex polyvalent metal ions, e.g. radionuclides, leading to soluble complexes of significant strength, thereby decreasing the sorption of these compounds to soils and sediments. The interaction of humic materials with radionuclides may significantly influence the availability and transport of the latter in the environment. Typically, studies along these lines have focussed almost exclusively on the radionuclides, whereas the actual role of the humic material has been elucidated only indirectly. In order directly to study the behavior of the naturally occurring organic macro-molecules in relation to the environmental fate of radionuclides, radio-labelled humic- and fulvic acids can advantageously be applied. Radio-labels such as 14C and 125I have successfully been covalently incorporated in humic- and fulvic-acids. Labelling of humic substances as well as preliminary migration studies are discussed

  18. Tetraphenylporphyrin as a protein label for triple detection analytical systems.

    Science.gov (United States)

    Konopińska, Kamila; Pietrzak, Mariusz; Mazur, Radosław; Malinowska, Elżbieta

    2015-12-01

    Porphyrins and metalloporphyrins are promising new protein labels that can be detected using multiple techniques; improving the reliability of the analysis and broadening the range of the linear response. Here, we investigate the potential of 5,10,15,20-tetraphenyl-21H,23H-porphyrin (Tpp) as a hybrid protein label. The electrochemical and optical properties of porphyrin conjugated with bovine serum albumin (BSA), chicken egg albumin (CEA) and immunoglobulin G (IgG) were determined and optimal conditions for Tpp-protein conjugation established. Model conjugates of carboxylated Tpp with BSA and short peptides were characterized using differential pulse voltammetry, UV-Vis spectrophotometry and spectrofluorimetry. These results reveal that Tpp is a promising molecule to be used in a triple detection protein labelling system. PMID:27441235

  19. Magnetic labelled HRP-polymer nanoparticles: A recyclable nanobiocatalyst

    Directory of Open Access Journals (Sweden)

    Khosravi Arezoo

    2013-01-01

    Full Text Available In this paper, the reusability and process stability of nano-reengineered horseradish peroxidase was investigated in fluorescence based sensing system for hydrogen peroxide determination as a model application. To this end, dendron macromolecules were attached to enzyme surface through bio-conjugation techniques. The resulted enzyme-polymer nanoparticles, with average size of 14(±2 nm, showed significant life time and thermal stability. For enzyme recovery and reusability purposes, the enzyme-polymer nanoparticles were labelled with magnetic nanoparticles with a labelling yield of 90%. These labelled enzyme molecules showed significant process stability up to 7 recycling period in a model sensing system. A linear calibration curve was obtained over the hydrogen peroxide concentrations ranging from 5×10-8 mol L-1 to 1×10-5 mol L-1 with detection limit of 1.3×10-9 mol L-1 for the sensing system under the optimal conditions.

  20. Oxygen labelled CO2

    International Nuclear Information System (INIS)

    Tests were carried out as to whether additional information concerning pulmonary gas exchange could be obtained from the application of oxygen labelled carbon dioxide. Single breath experiments were performed on two healthy subjects with 0.1 percent C16O18O and 2.8 percent C18O2 in the inspiratory gas. Breath-hold time was varied between 0.5-20s in different experiments. The 18O-concentration of the end-expired gas bi-exponentially decreased with increasing breath-hold time. The high and low rate constants 4s-1 and 0.12s-1 for C18O2 and 2.5s-1 and 0.87s-1 for C16O18O were derived, respectively. These results, together with model calculations, suggest: 1) the rapid disappearance of C18O2 from the alveolar space is primarily limited by diffusion, so that this isotopic species can be applied to quantify pulmonary diffusing conditions; 2) the lower disappearance rate of C16O18O is caused by a lower equilibration kinetics in blood, so that this isotopic species offers a possibility to study carbonic anhydrase activity of the red cells in vivo; 3) the slow phase of label decay is influenced by both alveolar dead space and carbonic anhydrase activity of the pulmonary tissues. Pathological dead spaces are expected to be sensitively detectable by C16O18O as well as by C18O2. (author). 4 refs.; 4 figs

  1. Towards single molecule switches.

    Science.gov (United States)

    Zhang, Jia Lin; Zhong, Jian Qiang; Lin, Jia Dan; Hu, Wen Ping; Wu, Kai; Xu, Guo Qin; Wee, Andrew T S; Chen, Wei

    2015-05-21

    The concept of using single molecules as key building blocks for logic gates, diodes and transistors to perform basic functions of digital electronic devices at the molecular scale has been explored over the past decades. However, in addition to mimicking the basic functions of current silicon devices, molecules often possess unique properties that have no parallel in conventional materials and promise new hybrid devices with novel functions that cannot be achieved with equivalent solid-state devices. The most appealing example is the molecular switch. Over the past decade, molecular switches on surfaces have been intensely investigated. A variety of external stimuli such as light, electric field, temperature, tunneling electrons and even chemical stimulus have been used to activate these molecular switches between bistable or even multiple states by manipulating molecular conformations, dipole orientations, spin states, charge states and even chemical bond formation. The switching event can occur either on surfaces or in break junctions. The aim of this review is to highlight recent advances in molecular switches triggered by various external stimuli, as investigated by low-temperature scanning tunneling microscopy (LT-STM) and the break junction technique. We begin by presenting the molecular switches triggered by various external stimuli that do not provide single molecule selectivity, referred to as non-selective switching. Special focus is then given to selective single molecule switching realized using the LT-STM tip on surfaces. Single molecule switches operated by different mechanisms are reviewed and discussed. Finally, molecular switches embedded in self-assembled monolayers (SAMs) and single molecule junctions are addressed. PMID:25757483

  2. Chains, clusters, inclusion compounds, paramagnetic labels, and organic rings

    CERN Document Server

    Zanello, P

    1994-01-01

    The role of stereochemistry to elucidate reaction patterns and physico-chemical properties in topical subjects ranging from inorganic to organic chemistry are treated in the fifth and final volume of this series. Detailed accounts are given to study: chaining in polyphosphates, electron-transfers in carbonyl clusters, inclusion of organometallic molecules in cyclodextrins, stereochemistry of paramagnetic metal complexes by labeling with nitroxyl radicals, stereocontrol in organic syntheses assisted by inorganic complexes.

  3. Physical activation of molecules

    International Nuclear Information System (INIS)

    A brief review of processes of physical activation of molecules on the basis of phenomena of electronic and vibrational excitation, electron polarization is presented. Consideration is given to activation by electron impact, photo-, magneto- and mechanoactivation, as well as to radiation activation, proceeding under the effect of high-power radiations (102-107 eV). The character of disturbance of molecules, participating in chemical reactions, under the effect of different types of ionizing radiation (α-particles, electrons, γ-quanta etc.) is discussed

  4. In silico labeling reveals the time-dependent label half-life and transit-time in dynamical systems

    Directory of Open Access Journals (Sweden)

    Maiwald Thomas

    2012-02-01

    Full Text Available Abstract Background Mathematical models of dynamical systems facilitate the computation of characteristic properties that are not accessible experimentally. In cell biology, two main properties of interest are (1 the time-period a protein is accessible to other molecules in a certain state - its half-life - and (2 the time it spends when passing through a subsystem - its transit-time. We discuss two approaches to quantify the half-life, present the novel method of in silico labeling, and introduce the label half-life and label transit-time. The developed method has been motivated by laboratory tracer experiments. To investigate the kinetic properties and behavior of a substance of interest, we computationally label this species in order to track it throughout its life cycle. The corresponding mathematical model is extended by an additional set of reactions for the labeled species, avoiding any double-counting within closed circuits, correcting for the influences of upstream fluxes, and taking into account combinatorial multiplicity for complexes or reactions with several reactants or products. A profile likelihood approach is used to estimate confidence intervals on the label half-life and transit-time. Results Application to the JAK-STAT signaling pathway in Epo-stimulated BaF3-EpoR cells enabled the calculation of the time-dependent label half-life and transit-time of STAT species. The results were robust against parameter uncertainties. Conclusions Our approach renders possible the estimation of species and label half-lives and transit-times. It is applicable to large non-linear systems and an implementation is provided within the PottersWheel modeling framework (http://www.potterswheel.de.

  5. Comparison of labels for Carafate in a gastric ulcer model

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate three radiolabels for the drug Carafate (basic aluminum sucrose octasulfate), which, when ingested orally, is believed to coat gastric ulcers and protect them from digestive enzymes to promote healing. In order to study the mode of action and residence time in the stomach using external imaging, a gamma-emitting label which is truly bound to the molecule is needed. Carafate has been radiolabeled with Se-75, In-111 (both chemically incorporated into the molecule) and with Tc-99m-HSA which physically adheres to Carafate. In the presence of stomach acid, Carafate polymerizes; when the labeled Carafates were mixed in vitro with 0.1N HCl, >90% of the radio-activity was associated with the polymer in the case of Se-75 and Tc-99m, but the In-111 label was less stable (25-35% bound to polymer). The three labeled preparations were administered orally to rats with gastric ulcers, and the transit of each was followed by gamma camera imaging. Gamma camera images confirmed radioactivity remaining at the ulcer site after unbound material had emptied from the stomach, and the focal activity persisted for >5 hours. The stomachs were then removed, washed and dissected at 5.5 hours and in vitro measurements of ulcer crater: normal stomach tissue radioactivity ratios averaged 15.4, 6.3, and 5.6 for the Se-75, In-111, and Tc-99m-HSA labels, respectively. Biodistribution studies of oral Se-75-Carafate in rats and pigs indicated that very little is absorbed from the GI tract and the distribution is similar to that of C-14-Carafate. It is concluded that Se-75 is the best marker for Carafate of these three gamma-emitting labels and Se-75-Carafate is suitable for studying the kinetics of the drug Carafate in human subjects

  6. Meat and Poultry Labeling Terms

    Science.gov (United States)

    ... Food Standards and Labels: The Facts Labeling and Marketing Information [ Top of Page ] OVEN PREPARED: Product is fully cooked and ready to eat. [ Top of Page ] YOUNG TURKEY: Turkeys of either sex that are less than 8 months of age according to present regulations. [ Top of Page ] Last ...

  7. Nutrition Marketing on Food Labels

    Science.gov (United States)

    Colby, Sarah E.; Johnson, LuAnn; Scheett, Angela; Hoverson, Bonita

    2010-01-01

    Objective: This research sought to determine how often nutrition marketing is used on labels of foods that are high in saturated fat, sodium, and/or sugar. Design and Setting: All items packaged with food labels (N = 56,900) in all 6 grocery stores in Grand Forks, ND were surveyed. Main Outcome Measure(s): Marketing strategy, nutrient label…

  8. [Investigation of the microstructure of biological systems by triplet label].

    Science.gov (United States)

    Kotel'niko, A I; Kuznetsov, S N; Fogel', V R; Likhtenshteĭn, G I

    1979-01-01

    A method for investigating the microstruct and dynamics of biological systems by means of triplet-excited molecules is suggested. The method is based on the phenomenon of triplet excitation disactivation by exchange-resonance triplet-triplet energy transfer to the acceptor or by intercombination conversion induced by interaction of an excited molecule with a paramagnetic center. The disactivation efficiency was measured by registrating the phosphorescense decay kinetics. The interaction of the triplet label eosin isothiocyanate, covalently coupled with albumine, lysozyme, sarcoplasmic reticulum membrane and Ca-Mg-dependent sarcoplasmic reticulum ATPase, with O2, the stable nitroxide radicals and ions of Mn2+ was investigated to analyse the potentialities of this method. As a model system the eosin phosphorescence quenching by the same quenchers in glycerine-aguaous solutions was studied. The method permits to investigate the microviscosity and microstructure of biological objects in the label attached region on interaction of the label with a sound-quencher with constants being 10(4) divided by 10(9) M-1 sec-1 and to measure the lateral diffusion of molecules in highly viscosity media (10 divided by 10(5) santypuas). PMID:223037

  9. A Better Carbon Footprint Label

    DEFF Research Database (Denmark)

    Thøgersen, John; Nielsen, Kristian S.

    2016-01-01

    expected, price and carbon footprint were negatively related to choice. Further, participants preferred organic to non-organic coffee and certification by a public authority. The effect of the carbon label is significantly stronger the more environmentally concerned the consumer is. Using colors to...... indicate relative carbon footprint significantly increases carbon label effectiveness. Hence, a carbon footprint label is more effective if it uses traffic light colors to communicate the product's relative performance.......Based on insights from behavioral economics, it is suggested to extend carbon footprint labeling with information about relative performance, using the well-known “traffic light” color scheme to communicate relative performance. To test this proposition, the impact of a carbon footprint label on...

  10. Sublinear distance labeling for sparse graphs

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Dahlgaard, Søren; Knudsen, Mathias Bæk Tejs; Porat, Ely

    A distance labeling scheme labels the $n$ nodes of a graph with binary strings such that, given the labels of any two nodes, one can determine the distance in the graph between the two nodes by looking only at the labels. A $D$-preserving distance labeling scheme only returns precise distances be...

  11. 21 CFR 201.71 - Magnesium labeling.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Magnesium labeling. 201.71 Section 201.71 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.71 Magnesium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the magnesium...

  12. Prebiologically Important Interstellar Molecules

    Science.gov (United States)

    Kuan, Y.-J.; Huang, H.-C.; Charnley, S. B.; Tseng, W.-L.; Snyder, L. E.; Ehrenfreund, P.; Kisiel, Z.; Thorwirth, S.; Bohn, R. K.; Wilson, T. L.

    2004-06-01

    Understanding the organic chemistry of molecular clouds, particularly the formation of biologically important molecules, is fundamental to the study of the processes which lead to the origin, evolution and distribution of life in the Galaxy. Determining the level of molecular complexity attainable in the clouds, and the nature of the complex organic material available to protostellar disks and the planetary systems that form from them, requires an understanding of the possible chemical pathways and is therefore a central question in astrochemistry. We have thus searched for prebiologically important molecules in the hot molecular cloud cores: Sgr B2(N-LMH), W51 e1/e2 and Orion-KL. Among the molecules searched: Pyrimidine is the unsubstituted ring analogue for three of the DNA and RNA bases. 2H-Azirine and Aziridine are azaheterocyclic compounds. And Glycine is the simplest amino acid. Detections of these interstellar organic molecular species will thus have important implications for Astrobiology. Our preliminary results indicate a tentative detection of interstellar glycine. If confirmed, this will be the first detection of an amino acid in interstellar space and will greatly strengthen the thesis that interstellar organic molecules could have played a pivotal role in the prebiotic chemistry of the early Earth.

  13. Atoms, Molecules, and Compounds

    CERN Document Server

    Manning, Phillip

    2007-01-01

    Explores the atoms that govern chemical processes. This book shows how the interactions between simple substances such as salt and water are crucial to life on Earth and how those interactions are predestined by the atoms that make up the molecules.

  14. Exotic helium molecules

    International Nuclear Information System (INIS)

    We study the photo-association of an ultracold cloud of magnetically trapped helium atoms: pairs of colliding atoms interact with one or two laser fields to produce a purely long range 4He2(23S1-23P0) molecule, or a 4He2(23S1-23S1) long range molecule. Light shifts in one photon photo-association spectra are measured and studied as a function of the laser polarization and intensity, and the vibrational state of the excited molecule. They result from the light-induced coupling between the excited molecule, and bound and scattering states of the interaction between two metastable atoms. Their analysis leads to the determination of the scattering length a = (7.2 ± 0.6) ruling collisions between spin polarized atoms. The two photon photo-association spectra show evidence of the production of polarized, long-range 4He2(23S1-23S1) molecules. They are said to be exotic as they are made of two metastable atoms, each one carrying a enough energy to ionize the other. The corresponding lineshapes are calculated and decomposed in sums and products of Breit-Wigner and Fano profiles associated to one and two photon processes. The experimental spectra are fit, and an intrinsic lifetime τ = (1.4 ± 0.3) μs is deduced. It is checked whether this lifetime could be limited by spin-dipole induced Penning autoionization. This interpretation requires that there is a quasi-bound state close to the dissociation threshold in the singlet interaction potential between metastable helium atoms for the theory to match the experiment. (author)

  15. OMG: Open Molecule Generator

    Directory of Open Access Journals (Sweden)

    Peironcely Julio E

    2012-09-01

    Full Text Available Abstract Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG, which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck.

  16. Bacterial invasion reconstructed molecule by molecule

    Energy Technology Data Exchange (ETDEWEB)

    Werner, James H [Los Alamos National Laboratory

    2009-01-01

    We propose to visualize the initial stages of bacterial infection of a human host cell with unmatched spatial and temporal resolution. This work will develop a new capability for the laboratory (super-resolution optical imaging), will test unresolved scientific hypotheses regarding host-pathogen interaction dynamics, and leverages state of the art 3D molecular tracking instrumentation developed recently by our group. There is much to be gained by applying new single molecule tools to the important and familiar problem of pathogen entry into a host cell. For example, conventional fluorescence microscopy has identified key host receptors, such as CD44 and {alpha}5{beta}1 integrin, that aggregate near the site of Salmonella typhimurium infection of human cells. However, due to the small size of the bacteria ({approx} 2 {micro}m) and the diffraction of the emitted light, one just sees a fluorescent 'blob' of host receptors that aggregate at the site of attachment, making it difficult to determine the exact number of receptors present or whether there is any particular spatial arrangement of the receptors that facilitates bacterial adhesion/entry. Using newly developed single molecule based super-resolution imaging methods, we will visualize how host receptors are directed to the site of pathogen adhesion and whether host receptors adopt a specific spatial arrangement for successful infection. Furthermore, we will employ our 3D molecular tracking methods to follow the injection of virulence proteins, or effectors, into the host cell by the pathogen Type III secretion system (TTSS). We expect these studies to provide mechanistic insights into the early events of pathogen infection that have here-to-fore been technically beyond our reach. Our Research Goals are: Goal 1--Construct a super-resolution fluorescence microscope and use this new capability to image the spatial distribution of different host receptors (e.g. CD44, as {alpha}5{beta}1 integrin) at the

  17. Biomedical applications of single molecule detection

    Science.gov (United States)

    Kelso, D. M.

    1997-05-01

    The search for increased sensitivity of bio-analytical techniques has recently shifted from signal generation to detection. While enzyme amplifiers and chemiluminescent reporters developed by chemists over the last two decades gradually moved detection limits to the attomol level, it has taken engineers only a few years to reach single- molecule sensitivity with the development of new instrumentation. A number of different approaches have successfully achieved single-molecule fluorescence detection including confocal and near-field scanning optical microscopy, photon-counting cameras, fluorescence- correlation and time-gated spectroscopy. They detect labels immobilized on substrates, diffusing in solution and flowing in electro-osmotic and hydrodynamically focused streams. Biotechnology has created numerous application s for single- molecule detection. In research labs, it can dramatically increase the rate of DNA sequencing, screen libraries for products of directed evolution, and characterize compounds in drug discovery programs. In medical diagnostics, ultra- sensitive detection technologies can be used for genetic screening, detection of infectious diseases, or multi- analyte profiles. It can be applied to immunoassays as well as DNA or RNA hybridization assays.

  18. Synthesis of coumarin or ferrocene labeled nucleosides via Staudinger ligation

    Directory of Open Access Journals (Sweden)

    Kois Pavol

    2006-11-01

    Full Text Available Abstract Background Reaction of azides with triaryl phosphines under mild conditions gives iminophosphoranes which can react with almost any kind of electrophilic reagent, e.g. aldehydes/ketones to form imines or esters to form amides. This so-called Staudinger ligation has been employed in a wide range of applications as a general tool for bioconjugation including specific labeling of nucleic acids. Results A new approach for the preparation of labeled nucleosides via intermolecular Staudinger ligation is described. Reaction of azidonucleosides with triphenylphosphine lead to iminophosphorane intermediates, which react subsequently with derivatives of coumarin or ferrocene to form coumarin or ferrocene labeled nucleosides. Fluorescent properties of coumarin labeled nucleosides are determined. Conclusion New coumarin and ferrocene labeled nucleosides were prepared via intermolecular Staudinger ligation. This reaction joins the fluorescent coumarin and biospecific nucleoside to the new molecule with promising fluorescent and electrochemical properties. The isolated yields of products depend on the structure of azidonucleoside and carboxylic acids. A detailed study of the kinetics of the Staudinger ligation with nucleoside substrates is in progress.

  19. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... Under Control Figuring Out Food Labels Healthy Food Shopping If My Child Has Food Allergies, What Should ... for Parents Figuring Out Food Labels Smart Supermarket Shopping Figuring Out Fat and Calories Food Labels Contact ...

  20. Single-molecule denaturation mapping of DNA in nanofluidic channels

    DEFF Research Database (Denmark)

    Reisner, Walter; Larsen, Niels Bent; Silahtaroglu, Asli;

    2010-01-01

    Here we explore the potential power of denaturation mapping as a single-molecule technique. By partially denaturing YOYO (R)-1-labeled DNA in nanofluidic channels with a combination of formamide and local heating, we obtain a sequence-dependent "barcode" corresponding to a series of local dips and...... peaks in the intensity trace along the extended molecule. We demonstrate that this structure arises from the physics of local denaturation: statistical mechanical calculations of sequence-dependent melting probability can predict the barcode to be observed experimentally for a given sequence....... Consequently, the technique is sensitive to sequence variation without requiring enzymatic labeling or a restriction step. This technique may serve as the basis for a new mapping technology ideally suited for investigating the long-range structure of entire genomes extracted from single cells....

  1. A systematization of spectral data on the methanol molecule

    Science.gov (United States)

    Akhlyostin, A. Yu.; Voronina, S. S.; Lavrentiev, N. A.; Privezentsev, A. I.; Rodimova, O. B.; Fazliev, A. Z.

    2015-11-01

    Problems underlying a systematization of spectral data on the methanol molecule are formulated. Data on the energy levels and vacuum wavenumbers acquired from the published literature are presented in the form of information sources imported into the W@DIS information system. Sets of quantum numbers and labels used to describe the CH3OH molecular states are analyzed. The set of labels is different from universally accepted sets. A system of importing the data sources into W@DIS is outlined. The structure of databases characterizing transitions in an isolated CH3OH molecule is introduced and a digital library of the relevant published literature is discussed. A brief description is given of an imported data quality analysis and representation of the results obtained in the form of ontologies for subsequent computer processing.

  2. Labelling GM-free Products

    DEFF Research Database (Denmark)

    Punt, Maarten; Venus, Thomas; Wesseler, Justus

    2016-01-01

    Food suppliers in the EU must comply with labelling regulations for genetically modified organisms (GMOs). However, excluded from mandatory labelling are food products derived from animals fed with GM feed (mainly GM soybean in the EU). Because of this labelling exemption, consumers are unable to...... limited. The results indicate that for switching to ‘GM-free’ production, long-term effects such as the creation of a positive image or differentiation from competitors are more important for dairy companies than short-term effects such as higher sales or profit....

  3. Sustainability labels on food products

    DEFF Research Database (Denmark)

    Grunert, Klaus G; Hieke, Sophie; Wills, Josephine

    2014-01-01

    This study investigates the relationship between consumer motivation, understanding and use of sustainability labels on food products (both environmental and ethical labels), which are increasingly appearing on food products. Data was collected by means of an online survey implemented in the UK...... types of information available on food labels or as use inferred from the results of a choice-based conjoint analysis. Hierarchical regression indicated that use is related to both motivation and understanding, and that both motivation, understanding and use are affected by demographic characteristics...

  4. New labels for radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, Susumu; Mukai, Minoru; Kato, Hirotoshi (National Inst. of Radiological Sciences, Chiba (Japan))

    1992-12-01

    In simulating radiotherapy, the bone and trachea identified by plain X-P and the other organs, such as the esophagus and bladder, outlined by contrast medium have so far been used as labels. However, irradiation with a high therapeutic ratio is required for an intracorporeal insertion of artificial labels that are identified by X-ray fluoroscopy. For this purpose, metal clips and seed dummies are available, although they cause artifacts in CT scans. Therefore, the authors are using an acupuncture needle and lipiodol for tracing as new artificial labels, since both are identified by X-ray fluoroscopy and CT scan and create few artifacts. (J.P.N.).

  5. New labels for radiation therapy

    International Nuclear Information System (INIS)

    In simulating radiotherapy, the bone and trachea identified by plain X-P and the other organs, such as the esophagus and bladder, outlined by contrast medium have so far been used as labels. However, irradiation with a high therapeutic ratio is required for an intracorporeal insertion of artificial labels that are identified by X-ray fluoroscopy. For this purpose, metal clips and seed dummies are available, although they cause artifacts in CT scans. Therefore, the authors are using an acupuncture needle and lipiodol for tracing as new artificial labels, since both are identified by X-ray fluoroscopy and CT scan and create few artifacts. (J.P.N.)

  6. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?

    International Nuclear Information System (INIS)

    Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [68Ga-DOTA,Tyr3]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its 111In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority. Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J. All peptides showed high affinities on hsst2, with the highest affinity for the GaIII-complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the GaIII peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all 67Ga-labelled peptides. Internalisation into HEK-sst3 was usually faster for the 111In-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [67Ga-DOTA,1-Nal3]octreotide in comparison to [111In-DOTA,1-Nal3]octreotide and [67Ga-DOTA,Tyr3]octreotide showed a significantly higher and receptor-mediated uptake of the two67Ga-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide. This study demonstrates that 67/68Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the 111In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further development for clinical studies. (orig.)

  7. Molecules without electrons

    International Nuclear Information System (INIS)

    Electrons are the glue that holds the atoms in molecules together. Without them the positive charges of nuclei would repel each other, and the world would be a much simpler place. But in the quest to gain control over matter at a fundamental level, physicists in Russia and Canada have come up with a way of binding charged nuclei without any electrons. Instead the researchers use intense laser light. (U.K.)

  8. Single Molecule Mechanochemistry

    Science.gov (United States)

    Li, Shaowei; Zhang, Yanxing; Ho, Wilson; Wu, Ruqian; Ruqian Wu, Yanxing Zhang Team; Wilson Ho, Shaowei Li Team

    Mechanical forces can be used to trigger chemical reactions through bending and stretching of chemical bonds. Using the reciprocating movement of the tip of a scanning tunneling microscope (STM), mechanical energy can be provided to a single molecule sandwiched between the tip and substrate. When the mechanical pulse center was moved to the outer ring feature of a CO molecule, the reaction rate was significantly increased compared with bare Cu surface and over Au atoms. First, DFT calculations show that the presence of CO makes the Cu cavity more attractive toward H2 Second, H2 prefers the horizontal adsorption geometry in the Cu-Cu and Au-Cu cavities and no hybridization occurs between the antibonding states of H2 and states of Cu atoms. While H2 loses electrons from its bonding state in all three cavities, the filling of its anti-bonding state only occurs in the CO-Cu cavity. Both make the CO-Cu cavity much more effectively to chop the H2 molecule. Work was supported by the National Science Foundation Center for Chemical Innovation on Chemistry at the Space-Time Limit (CaSTL) under Grant No. CHE-1414466.

  9. Photonic Molecule Lasers Revisited

    Science.gov (United States)

    Gagnon, Denis; Dumont, Joey; Déziel, Jean-Luc; Dubé, Louis J.

    2014-05-01

    Photonic molecules (PMs) formed by coupling two or more optical resonators are ideal candidates for the fabrication of integrated microlasers, photonic molecule lasers. Whereas most calculations on PM lasers have been based on cold-cavity (passive) modes, i.e. quasi-bound states, a recently formulated steady-state ab initio laser theory (SALT) offers the possibility to take into account the spectral properties of the underlying gain transition, its position and linewidth, as well as incorporating an arbitrary pump profile. We will combine two theoretical approaches to characterize the lasing properties of PM lasers: for two-dimensional systems, the generalized Lorenz-Mie theory will obtain the resonant modes of the coupled molecules in an active medium described by SALT. Not only is then the theoretical description more complete, the use of an active medium provides additional parameters to control, engineer and harness the lasing properties of PM lasers for ultra-low threshold and directional single-mode emission. We will extend our recent study and present new results for a number of promising geometries. The authors acknowledge financial support from NSERC (Canada) and the CERC in Photonic Innovations of Y. Messaddeq.

  10. NIR fluorescent silica nanoparticles as reporting labels in bioanalytical applications

    Science.gov (United States)

    Patonay, Gabor; Henary, Maged; Chapman, Gala; Emer, Kyle; Crow, Sydney

    2015-03-01

    The use of the NIR spectral region (650-900 nm) for bioanalytical and biomedical analyses is advantageous due to the inherently lower background interference in biological matrices and the high molar absorptivities of NIR chromophores. There are several different groups of NIR fluorescing dye are available for bioanalytical applications. One of these groups, NIR carbocyanines are increasingly used in analytical, bioanalytical and medical applications. These dyes can be used as reporter labels for sensitive bioanalytical use, such as immunochemistry. Due to the spectroscopic sensitivity of NIR carbocyanines for polarity changes in the microenvironment fluorescence quantum yield can vary significantly dependent on the microenvironment. NIR dyes can have relatively low fluorescent quantum yields as compared to visible fluorophores, especially in aqueous buffers but the lower quantum yield is compensated for by a much higher molar absorptivity. The fluorescence intensity of NIR reporting labels can significantly be increased by enclosing several dye molecules in silica nanoparticles. Incorporation of NIR dyes in silica nanoparticles creates a unique challenge as these dyes can be unstable under certain chemical conditions present during silica nanoparticles syntheses. In addition, self quenching may also become a problem for carbocyanines at higher a concentrations that typically found inside of NIR dye loaded silica nanoparticles. Dyes possessing high Stokes' shift can significantly reduce this problem. NIR carbocyanines are uniquely positioned for achieving this goal using a synthetic route that substitutes meso position halogens in NIR fluorescent carbocyanines with a linker containing amino moiety, which can also serve as a linker for covalently attaching the dye molecule to the nanoparticle backbone. The resulting silica nanoparticles can contain a large number of NIR dyes dependent on their size. For example some NIR fluorescent silica nanoparticle labels

  11. Quality control of labelled compounds

    International Nuclear Information System (INIS)

    Some advantages and disadvantages of methods used for quality control of organic labelled compounds (131I, 14C) are shortly discussed. The methods used are electrophoresis, ultraviolet and infrared spectrometry, radiogas and thin-layer chromatography. (author)

  12. Labeling of receptor ligands with bromine radionuclides. Progress report, March 1, 1981-February 29, 1984

    International Nuclear Information System (INIS)

    We have developed techniques to label several types of organic molecules with radiobromine. We have emphasized techniques to label ligands for the estrogen receptor and have studied two brominated compounds in rat models. One of these compounds has been studied in a limited number of patients and estrogen containing tumors visualized by nuclear medicine imaging. We have recently expanded the size of the work to label receptor ligands with fluorine-18 and have carried out preliminary animal studies which suggest that a clinically useful compound can be prepared. In addition to the receptor studies, we have collaborated in assessing 77Br-labeled compounds as therapeutic agents and in studying 77Br-labeled compounds using perturbed angular correlation techniques

  13. Detection of the cancer marker CD146 expression in melanoma cells with semiconductor quantum dot label.

    Science.gov (United States)

    Zheng, Hong; Chen, Guangchun; DeLouise, Lisa A; Lou, Ziyang

    2010-08-01

    The use of highly specific and highly sensitive quantum dots immunofluorescent label is a promising approach for biomedical imaging in cancer cells. Human melanoma cell adhesion molecule CD146, overexpressed on the surface of melanoma cells, is an important target for melanoma diagnostics. We synthesized PEG-COOH capped highly fluorescent CdSe/ZnS QDs and conjugated them with streptavidin to prepare QD-SA label. Then, we used QD-SA to link with biotinylated goat anti-mouse IgG and mouse anti-human CD146 to label CD146 overexpressed on live and fixed cells by FACS and Confocal microscopy. Labeling of target cells was shown to have high brightness, photostability, and specificity. Advantages of QD conjugates over FITC conjugates are discussed. The results indicate that construction based on QD-SA label, biotinylated IgG and CD146 antibody can be successfully used for detection of melanoma cells for biomedical applications. PMID:21323102

  14. Astatine-211-Labeled Targeted Radiotherapeutics: An Update

    International Nuclear Information System (INIS)

    The heavy halogen 211At was first proposed for use in α-particle targeted radiotherapy more than 30 years ago and continues to be one of the most promising radionuclides for this purpose. Although its 7.2-h half life is not ideal for intravenously administered whole antibodies, it is compatible with the pharmacokinetics of antibody fragments, peptides, aptamers and organic molecules. Its diverse chemistry allows its incorporation into a wide array of targeting vehicles, relying on its chemical similarity to iodine to provide a useful point of departure. On the other hand, the relatively low carbon-astatine bond strength is challenging. In common with the other α-emitters being discussed at this symposium, lack of reliable availability is one of the biggest hurdles in the use of 211At for targeted radiotherapy. However, in the case of 211At, it is not a question of production cost or availability of target material, because 211At can be produced in reasonable yield from natural bismuth targets. Rather, the difficulty is the lack of cyclotrons equipped with the medium energy α-particle beams required for its production. If the infrastructure for producing 211At is to be improved to the stage where 211At-labeled radiopharmaceuticals can have a meaningful impact, several developments must occur. First, the ability to produce clinically relevant levels of 211At that can be shipped to remote locations in chemically tractable form must be demonstrated. Approaches under consideration include compensating for radiolysis-mediated effects and the consideration of alternative chemistries. Second, strategies for compensating for heterogeneities in dose deposition must be developed, hopefully in a way that is compatible with approval for human use. And third, it is essential that more clinical trials be performed with 211At-labeled therapeutics, particularly in settings of minimum residual disease where the radiobiological advantages of α-particles can be best exploited. Our

  15. Transmembrane signaling through major histocompatibility complex (MHC) encoded molecules

    International Nuclear Information System (INIS)

    The importance of the major histocompatibility complex (MHC) encoded molecules has traditionally been ascribed to the role these molecules play as restriction elements for T lymphocytes. This is, in order for T cell activation to occur the T cell must recognize antigen in association with MHC molecules. More controversial, however, is the potential role MHC molecules play as signal transducing receptors/acceptors to the B lymphocyte. In other words, do class II MHC molecules (Ia antigens) actively transduce a signal to the B cell which drives its differentiation into an antibody secreting cell? Two approaches to this question are described. The first involves biochemical characterization of those molecules which consistently copurify with I-A/sup k/ by two dimensional gel electrophoresis. The second approach utilizes two types of analyses: first, an examination of the biochemical changes which occur in the cell as a result of Ia ligation; and second, analysis of changes in the B cell's physiological response as a result of Ia perturbation. Molecules were examined which may couple the antigen binding event in the B lymphocyte to the antigen driven signal transduction cascade which ultimately leads to immunoglobulin secretion. In these experiments, cells were labelled with [32P] and stimulated cells with phorbol myristate acetate. The membrane form of immunoglobulin was then isolated from detergent lysates of whole cells and passed over an anti-k affinity column. The eluates were analyzed by SDS-PAGE

  16. NMR studies of two spliced leader RNAs using isotope labeling

    Energy Technology Data Exchange (ETDEWEB)

    Lapham, J.; Crothers, D.M. [Yale Univ., New Haven, CT (United States)

    1994-12-01

    Spliced leader RNAs are a class of RNA molecules (<200 nts) involved in the trans splicing of messenger RNA found in trypanosomes, nematodes, and other lower eukaryotes. The spliced leader RNA from the trypanosome Leptomonas Collosoma exists in two alternate structural forms with similar thermal stabilities. The 54 nucleotides on the 5{prime} end of the SL molecule is structurally independent from the 3{prime} half of the RNA, and displays the two structural forms. Furthermore, the favored of the two structures was shown to contain anomalous nuclease sensitivity and thermal stability features, which suggests that there may be tertiary interactions between the splice site and other nucleotides in the 5{prime} end. Multidimensional NMR studies are underway to elucidate the structural elements present in the SL RNAs that give rise to their physical properties. Two spliced leader sequences have been studied. The first, the 54 nucleotides on the 5{prime} end of the L. Collosoma sequence, was selected because of earlier studies in our laboratory. The second sequence is the 5{prime} end of the trypanosome Crithidia Fasciculata, which was chosen because of its greater sequence homology to other SL sequences. Given the complexity of the NMR spectra for RNA molecules of this size, we have incorporated {sup 15}N/{sup 13}C-labeled nucleotides into the RNA. One of the techniques we have developed to simplify the spectra of these RNA molecules is isotope labeling of specific regions of the RNA. This has been especially helpful in assigning the secondary structure of molecules that may be able to adopt multiple conformations. Using this technique one can examine a part of the molecule without spectral interference from the unlabeled portion. We hope this approach will promote an avenue for studying the structure of larger RNAs in their native surroundings.

  17. LabeledIn: cataloging labeled indications for human drugs.

    Science.gov (United States)

    Khare, Ritu; Li, Jiao; Lu, Zhiyong

    2014-12-01

    Drug-disease treatment relationships, i.e., which drug(s) are indicated to treat which disease(s), are among the most frequently sought information in PubMed®. Such information is useful for feeding the Google Knowledge Graph, designing computational methods to predict novel drug indications, and validating clinical information in EMRs. Given the importance and utility of this information, there have been several efforts to create repositories of drugs and their indications. However, existing resources are incomplete. Furthermore, they neither label indications in a structured way nor differentiate them by drug-specific properties such as dosage form, and thus do not support computer processing or semantic interoperability. More recently, several studies have proposed automatic methods to extract structured indications from drug descriptions; however, their performance is limited by natural language challenges in disease named entity recognition and indication selection. In response, we report LabeledIn: a human-reviewed, machine-readable and source-linked catalog of labeled indications for human drugs. More specifically, we describe our semi-automatic approach to derive LabeledIn from drug descriptions through human annotations with aids from automatic methods. As the data source, we use the drug labels (or package inserts) submitted to the FDA by drug manufacturers and made available in DailyMed. Our machine-assisted human annotation workflow comprises: (i) a grouping method to remove redundancy and identify representative drug labels to be used for human annotation, (ii) an automatic method to recognize and normalize mentions of diseases in drug labels as candidate indications, and (iii) a two-round annotation workflow for human experts to judge the pre-computed candidates and deliver the final gold standard. In this study, we focused on 250 highly accessed drugs in PubMed Health, a newly developed public web resource for consumers and clinicians on prevention

  18. A novel {sup 18}F-labeled two-helix scaffold protein for PET imaging of HER2-positive tumor

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Zheng; Ren, Gang; Jiang, Lei; Liu, Hongguang; Cheng, Zhen [Stanford University, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford Cancer Center, Bio-X Program, Stanford, CA (United States); Webster, Jack M.; Zhang, Rong; Syud, Faisal [General Electric Company, Global Research, Niskayuna, NY (United States); Namavari, Mohammad; Gambhir, Sanjiv S. [Stanford University, MIPS, Departments of Radiology and Bioengineering, Stanford Cancer Center, Bio-X Program, Stanford, CA (United States)

    2011-11-15

    Two-helix scaffold proteins ({proportional_to} 5 kDa) against human epidermal growth factor receptor type 2 (HER2) have been discovered in our previous work. In this research we aimed to develop an {sup 18}F-labeled two-helix scaffold protein for positron emission tomography (PET) imaging of HER2-positive tumors. An aminooxy-functionalized two-helix peptide (AO-MUT-DS) with high HER2 binding affinity was synthesized through conventional solid phase peptide synthesis. The purified linear peptide was cyclized by I{sub 2} oxidation to form a disulfide bridge. The cyclic peptide was then conjugated with a radiofluorination synthon, 4-{sup 18}F-fluorobenzyl aldehyde ({sup 18}F-FBA), through the aminooxy functional group at the peptide N terminus (30% yield, non-decay corrected). The binding affinities of the peptides were analyzed by Biacore analysis. Cell uptake assay of the resulting PET probe, {sup 18}F-FBO-MUT-DS, was performed at 37 C. {sup 18}F-FBO-MUT-DS with high specific activity (20-32 MBq/nmol, 88-140 {mu}Ci/{mu}g, end of synthesis) was injected into mice xenograft model bearing SKOV3 tumor. MicroPET and biodistribution and metabolic stability studies were then conducted. Cell uptake assays showed high and specific cell uptake ({proportional_to}12% applied activity at 1 h) by incubation of {sup 18}F-FBO-MUT-DS with HER2 high-expressing SKOV3 ovarian cancer cells. The affinities (K{sub D}) of AO-MUT-DS and FBO-MUT-DS as tested by Biacore analysis were 2 and 1 nM, respectively. In vivo small animal PET demonstrated fast tumor targeting, high tumor accumulation, and good tumor to normal tissue contrast of {sup 18}F-FBO-MUT-DS. Biodistribution studies further revealed that the probe had excellent tumor uptake (6.9%ID/g at 1 h post-injection) and was cleared through both liver and kidneys. Co-injection of the probe with 500 {mu}g of HER2 Affibody protein reduced the tumor uptake (6.9 vs 1.8%ID/g, p < 0.05). F-FBO-MUT-DS displays excellent HER2 targeting ability

  19. A novel 18F-labeled two-helix scaffold protein for PET imaging of HER2-positive tumor

    International Nuclear Information System (INIS)

    Two-helix scaffold proteins (∝ 5 kDa) against human epidermal growth factor receptor type 2 (HER2) have been discovered in our previous work. In this research we aimed to develop an 18F-labeled two-helix scaffold protein for positron emission tomography (PET) imaging of HER2-positive tumors. An aminooxy-functionalized two-helix peptide (AO-MUT-DS) with high HER2 binding affinity was synthesized through conventional solid phase peptide synthesis. The purified linear peptide was cyclized by I2 oxidation to form a disulfide bridge. The cyclic peptide was then conjugated with a radiofluorination synthon, 4-18F-fluorobenzyl aldehyde (18F-FBA), through the aminooxy functional group at the peptide N terminus (30% yield, non-decay corrected). The binding affinities of the peptides were analyzed by Biacore analysis. Cell uptake assay of the resulting PET probe, 18F-FBO-MUT-DS, was performed at 37 C. 18F-FBO-MUT-DS with high specific activity (20-32 MBq/nmol, 88-140 μCi/μg, end of synthesis) was injected into mice xenograft model bearing SKOV3 tumor. MicroPET and biodistribution and metabolic stability studies were then conducted. Cell uptake assays showed high and specific cell uptake (∝12% applied activity at 1 h) by incubation of 18F-FBO-MUT-DS with HER2 high-expressing SKOV3 ovarian cancer cells. The affinities (KD) of AO-MUT-DS and FBO-MUT-DS as tested by Biacore analysis were 2 and 1 nM, respectively. In vivo small animal PET demonstrated fast tumor targeting, high tumor accumulation, and good tumor to normal tissue contrast of 18F-FBO-MUT-DS. Biodistribution studies further revealed that the probe had excellent tumor uptake (6.9%ID/g at 1 h post-injection) and was cleared through both liver and kidneys. Co-injection of the probe with 500 μg of HER2 Affibody protein reduced the tumor uptake (6.9 vs 1.8%ID/g, p 18F-based PET probes. (orig.)

  20. Multicolor protein labeling in living cells using mutant β-lactamase-tag technology.

    Science.gov (United States)

    Watanabe, Shuji; Mizukami, Shin; Hori, Yuichiro; Kikuchi, Kazuya

    2010-12-15

    Protein labeling techniques using small molecule probes have become important as practical alternatives to the use of fluorescent proteins (FPs) in live cell imaging. These labeling techniques can be applied to more sophisticated fluorescence imaging studies such as pulse-chase imaging. Previously, we reported a novel protein labeling system based on the combination of a mutant β-lactamase (BL-tag) with coumarin-derivatized probes and its application to specific protein labeling on cell membranes. In this paper, we demonstrated the broad applicability of our BL-tag technology to live cell imaging by the development of a series of fluorescence labeling probes for this technology, and the examination of the functions of target proteins. These new probes have a fluorescein or rhodamine chromophore, each of which provides enhanced photophysical properties relative to coumarins for the purpose of cellular imaging. These probes were used to specifically label the BL-tag protein and could be used with other small molecule fluorescent probes. Simultaneous labeling using our new probes with another protein labeling technology was found to be effective. In addition, it was also confirmed that this technology has a low interference with respect to the functions of target proteins in comparison to GFP. Highly specific and fast covalent labeling properties of this labeling technology is expected to provide robust tools for investigating protein functions in living cells, and future applications can be improved by combining the BL-tag technology with conventional imaging techniques. The combination of probe synthesis and molecular biology techniques provides the advantages of both techniques and can enable the design of experiments that cannot currently be performed using existing tools. PMID:20961132

  1. Bridging the gap between single molecule and ensemble methods for measuring lateral dynamics in the plasma membrane

    DEFF Research Database (Denmark)

    Christensen, Eva Arnspang; Schwartzentruber, J.; Clausen, M. P.;

    2013-01-01

    comparing the results for a biotinylated lipid labeled at high densities with Atto647N-strepatvidin (sAv) or sparse densities with sAv-QDs. In this latter case, we see that the recovered diffusion rate is two-fold greater for the same lipid and in the same cell-type when labeled with Atto647N-sAv as...... compared to sAv-QDs. This data demonstrates that kICS can be used for analysis of single molecule data and furthermore can bridge between samples with a labeling densities ranging from single molecule to ensemble level measurements....

  2. Watching single molecules dance

    Science.gov (United States)

    Mehta, Amit Dinesh

    Molecular motors convert chemical energy, from ATP hydrolysis or ion flow, into mechanical motion. A variety of increasingly precise mechanical probes have been developed to monitor and perturb these motors at the single molecule level. Several outstanding questions can be best approached at the single molecule level. These include: how far does a motor progress per energy quanta consumed? how does its reaction cycle respond to load? how many productive catalytic cycles can it undergo per diffusional encounter with its track? and what is the mechanical stiffness of a single molecule connection? A dual beam optical trap, in conjunction with in vitro ensemble motility assays, has been used to characterize two members of the myosin superfamily: muscle myosin II and chick brain myosin V. Both move the helical polymer actin, but myosin II acts in large ensembles to drive muscle contraction or cytokinesis, while myosin V acts in small numbers to transport vesicles. An optical trapping apparatus was rendered sufficiently precise to identify a myosin working stroke with 1nm or so, barring systematic errors such as those perhaps due to random protein orientations. This and other light microscopic motility assays were used to characterize myosin V: unlike myosin II this vesicle transport protein moves through many increments of travel while remaining strongly bound to a single actin filament. The step size, stall force, and travel distance of myosin V reveal a remarkably efficient motor capable of moving along a helical track for over a micrometer without significantly spiraling around it. Such properties are fully consistent with the putative role of an organelle transport motor, present in small numbers to maintain movement over long ranges relative to cellular size scales. The contrast between myosin II and myosin V resembles that between a human running on the moon and one walking on earth, where the former allows for faster motion when in larger ensembles but for less

  3. Single-DNA-molecule trapping with silicon nanotweezers using pulsed dielectrophoresis

    International Nuclear Information System (INIS)

    DNA manipulation based on dielectrophoresis between microfabricated electrodes is one of the most efficient methods for the physical handling of molecules. Dielectrophoresis is routinely used for stretching and trapping DNA molecules between the opposing tips of silicon nanotweezers. However, the precise number of trapped molecules is difficult to predict, as a continuous application of ac voltage continually attracts the molecules while the electric-field-induced fluid flow prevents them from bridging the tips. To circumvent this difficulty, the dielectrophoresis signal is applied during very short intervals. In this pulsed mode, the electrohydrodynamic fluid flow is lessened and the molecule trapping success rate is greatly enhanced. A fluorescently labeled single λ-DNA molecule was successfully stretched and captured by the silicon nanotweezers with 50 ms pulses of a 1 MHz, 1 MV m−1 ac dielectrophoresis voltage. This single-molecule trapping between the tweezers' tips is monitored, in real time, under fluorescence imaging

  4. Ultra-cold molecule production.

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez-Serrano, Jamie; Chandler, David W.; Strecker, Kevin; Rahn, Larry A.

    2005-12-01

    The production of Ultra-cold molecules is a goal of many laboratories through out the world. Here we are pursuing a unique technique that utilizes the kinematics of atomic and molecular collisions to achieve the goal of producing substantial numbers of sub Kelvin molecules confined in a trap. Here a trap is defined as an apparatus that spatially localizes, in a known location in the laboratory, a sample of molecules whose temperature is below one degree absolute Kelvin. Further, the storage time for the molecules must be sufficient to measure and possibly further cool the molecules. We utilize a technique unique to Sandia to form cold molecules from near mass degenerate collisions between atoms and molecules. This report describes the progress we have made using this novel technique and the further progress towards trapping molecules we have cooled.

  5. Magnetic field modification of ultracold molecule-molecule collisions

    OpenAIRE

    Tscherbul, T. V.; Suleimanov, Yu. V.; Aquilanti, V.; Krems, R.V.

    2008-01-01

    We present an accurate quantum mechanical study of molecule-molecule collisions in the presence of a magnetic field. The work focusses on the analysis of elastic scattering and spin relaxation in collisions of O2(3Sigma_g) molecules at cold (~0.1 K) and ultracold (~10^{-6} K) temperatures. Our calculations show that magnetic spin relaxation in molecule-molecule collisions is extremely efficient except at magnetic fields below 1 mT. The rate constant for spin relaxation at T=0.1 K and a magnet...

  6. Label-Free Direct Electronic Detection of Biomolecules with Amorphous Silicon Nanostructures

    OpenAIRE

    Lund, John; Mehta, Ranjana; Parviz, Babak A.

    2006-01-01

    We present the fabrication and characterization of a nano-scale sensor made of amorphous silicon for the label-free, electronic detection of three classes of biologically important molecules: ions, oligonucleotides, and proteins. The sensor structure has an active element which is a 50 nm wide amorphous silicon semicircle and has a total footprint of less than 4 μm2. We demonstrate the functionalization of the sensor with receptor molecules and the electronic detection of three targets: H+ io...

  7. Distribution of epinemin in colloidal gold-labelled, quick-frozen, deep- etched cytoskeletons

    OpenAIRE

    1984-01-01

    In this study I describe the ultrastructural distribution of epinemin (Lawson, D., 1983, J. Cell Biol., 97:1891-1905) in antibody-labelled, helium-cooled, quick-frozen, deep-etched cytoskeletons. This technique reveals that epinemin is expressed asymmetrically at discrete sites on the vimentin core polymer and that usually one (occasionally two or three) antiepinemin molecules are found at each of these discrete foci. Single receptor-bound antiepinemin (IgM) molecules are easily identified in...

  8. Mindboggle: Automated brain labeling with multiple atlases

    International Nuclear Information System (INIS)

    To make inferences about brain structures or activity across multiple individuals, one first needs to determine the structural correspondences across their image data. We have recently developed Mindboggle as a fully automated, feature-matching approach to assign anatomical labels to cortical structures and activity in human brain MRI data. Label assignment is based on structural correspondences between labeled atlases and unlabeled image data, where an atlas consists of a set of labels manually assigned to a single brain image. In the present work, we study the influence of using variable numbers of individual atlases to nonlinearly label human brain image data. Each brain image voxel of each of 20 human subjects is assigned a label by each of the remaining 19 atlases using Mindboggle. The most common label is selected and is given a confidence rating based on the number of atlases that assigned that label. The automatically assigned labels for each subject brain are compared with the manual labels for that subject (its atlas). Unlike recent approaches that transform subject data to a labeled, probabilistic atlas space (constructed from a database of atlases), Mindboggle labels a subject by each atlas in a database independently. When Mindboggle labels a human subject's brain image with at least four atlases, the resulting label agreement with coregistered manual labels is significantly higher than when only a single atlas is used. Different numbers of atlases provide significantly higher label agreements for individual brain regions. Increasing the number of reference brains used to automatically label a human subject brain improves labeling accuracy with respect to manually assigned labels. Mindboggle software can provide confidence measures for labels based on probabilistic assignment of labels and could be applied to large databases of brain images

  9. 49 CFR 172.407 - Label specifications.

    Science.gov (United States)

    2010-10-01

    ... line outer border to meet the requirements of § 172.406(d) of this subpart. (c) Size. (1) Each diamond..., numbers, and border must be shown in black on a label except that— (i) White may be used on a label with a... the CORROSIVE label. (iii) White may be used for the symbol for the ORGANIC PEROXIDE label. (3)...

  10. Radiation dose estimates for carbon-11-labelled PET tracers

    International Nuclear Information System (INIS)

    Introduction: Carbon-11-labelled positron emission tomography (PET) tracers commonly used in biomedical research expose subjects to ionising radiation. Dosimetry is the measurement of radiation dose, but also commonly refers to the estimation of health risk associated with ionising radiation. This review describes radiation dosimetry of carbon-11-labelled molecules in the context of current PET research and the most widely used regulatory guidelines. Methods: A MEDLINE literature search returned 42 articles; 32 of these were based on human PET data dealing with radiation dosimetry of carbon-11 molecules. Radiation burden expressed as effective dose and maximum absorbed organ dose was compared between tracers. Results: All but one of the carbon-11-labelled PET tracers have an effective dose under 9 μSv/MBq, with a mean of 5.9 μSv/MBq. Data show that serial PET scans in a single subject are feasible for the majority of radiotracers. Conclusion: Although differing in approach, the two most widely used regulatory frameworks (those in the USA and the EU) do not differ substantially with regard to the maximum allowable injected activity per PET study. The predictive validity of animal dosimetry models is critically discussed in relation to human dosimetry. Finally, empirical PET data are related to human dose estimates based on homogenous distribution, generic models and maximum cumulated activities. Despite the contribution of these models to general risk estimation, human dosimetry studies are recommended where continued use of a new PET tracer is foreseen.

  11. Passing Current through Touching Molecules

    DEFF Research Database (Denmark)

    Schull, G.; Frederiksen, Thomas; Brandbyge, Mads;

    2009-01-01

    The charge flow from a single C-60 molecule to another one has been probed. The conformation and electronic states of both molecules on the contacting electrodes have been characterized using a cryogenic scanning tunneling microscope. While the contact conductance of a single molecule between two...

  12. Efficient single molecule detection and single molecule photochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Affleck, R.L.; Ambrose, W.P.; Goodwin, P.M. [Los Alamos National Lab., NM (United States)] [and others

    1996-12-31

    Single molecule detection efficiencies greater than 90% in flowing sample streams can be attained by confining the sample to the center of the excitation laser beam and photobleaching the reagent stream immediately before it enters the detection flow cell. Photolysis of single molecules of B-Phycoerythrin dissolved in aqueous solution is observed as an abrupt cessation of the fluorescence from these molecules as they flow through {approximately}40 pl probe volume. An analysis of the survival times of individual molecules in the laser beams yields the photodestruction quantum yield of the molecule. Photon pair correlation measurements of the fluorescence detected from single B-PE molecules demonstrate that the molecule fluoresces from only one bilin chromophore at a time.

  13. Advances in 99mTc-labeling of antibodies

    International Nuclear Information System (INIS)

    Several methods have been developed to label antibodies with 99mTc. Direct labeling results in 99mTc binding to multiple sites of various affinities that are often weaker than the binding to strong chelating agents. Attempts to overcome this disadvantage involve conjugation of strong chelating agents to the antibodies. While stability is usually enhanced, this approach suffers from alteration of antibody properties as well as non-specific binding of 99mTc to the antibody instead of to the conjugation chelating agent. This has been of concern for studies with DTPA as the chelating agent. In this study the loss of 99mTc by N2S2 challenge shows that a fraction to the 99mTc is nonspecifically bound to the antibody. An advantage of the approach of labeling antibodies containing a bifunctional chelating agent is the simplicity of the labeling procedure and the apparent high yields that in reality are the sum of chelating agent and non-specifically bound radioactivity. The last approach described in our work of conjugation of a preformed chelate has advantages of characterizable 99mTc complex chemistry and conjugation by standard protein derivatization chemistry. Slow chelation kinetics can be overcome in the small molecule stage and then conjugation performed under mild conditions with respect to the antibody of fragments. This approach, however, suffers from greater complexity of the labeling process including multiple steps, purifications and non-quantitative yields. The use of ligands for 99mTc in which the complexes are of high stability and predictable chemistry is likely to result in eventual optimal labeling technologies. Processes which are non-specific may work in some cases, but are likely to present difficulties in optimization and general applicability from antibody to antibody. (orig.)

  14. Radio labeling with pre-assigned frequencies

    OpenAIRE

    Bodlaender, H.L.; Broersma, H.J.; Fomin, F.V.; Pyatkin, A.V.; Woeginer, G.J.

    2007-01-01

    A radio labeling of a graph G is an assignment of pairwise distinct, positive integer labels to the vertices of G such that labels of adjacent vertices differ by at least 2. The radio labeling problem (RL) consists in determining a radio labeling that minimizes the maximum label that is used (the so-called span of the labeling). RL is a well-studied problem, mainly motivated by frequency assignment problems in which transmitters are not allowed to operate on the same frequency channel. We con...

  15. Radio labeling with pre-assigned frequencies

    OpenAIRE

    Bodlaender, H.L.; Broersma, H.J.; Fomin, F.V.; Pyatkin, A.V.; Woeginger, G.J.

    2002-01-01

    A radio labeling of a graph $G$ is an assignment of pairwise distinct, positive integer labels to the vertices of $G$ such that labels of adjacent vertices differ by at least $2$. The radio labeling problem (\\mbox{\\sc RL}) consists in determining a radio labeling that minimizes the maximum label that is used (the so-called span of the labeling). \\mbox{\\sc RL} is a well-studied problem, mainly motivated by frequency assignment problems in which transmitters are not allowed to operate on the sa...

  16. Photoaffinity Labeling of Plasma Proteins

    Directory of Open Access Journals (Sweden)

    Masaki Otagiri

    2013-11-01

    Full Text Available Photoaffinity labeling is a powerful technique for identifying a target protein. A high degree of labeling specificity can be achieved with this method in comparison to chemical labeling. Human serum albumin (HSA and α1-acid glycoprotein (AGP are two plasma proteins that bind a variety of endogenous and exogenous substances. The ligand binding mechanism of these two proteins is complex. Fatty acids, which are known to be transported in plasma by HSA, cause conformational changes and participate in allosteric ligand binding to HSA. HSA undergoes an N-B transition, a conformational change at alkaline pH, that has been reported to result in increased ligand binding. Attempts have been made to investigate the impact of fatty acids and the N-B transition on ligand binding in HSA using ketoprofen and flunitrazepam as photolabeling agents. Meanwhile, plasma AGP is a mixture of genetic variants of the protein. The photolabeling of AGP with flunitrazepam has been utilized to shed light on the topology of the protein ligand binding site. Furthermore, a review of photoaffinity labeling performed on other major plasma proteins will also be discussed. Using a photoreactive natural ligand as a photolabeling agent to identify target protein in the plasma would reduce non-specific labeling.

  17. Radioisotope method for leucocyte labelling

    International Nuclear Information System (INIS)

    Whole blood leukocytes were labelled with 99mTc-sulphocolloid, which was selectively deposited in phagocytizing polymorphonuclear cells. To achieve optimal phagocytosis, the authors prepared 99mTc sulphocoloid from a Bulgarian kit. The required size of the colloid particles (1,2 μm) was achieved after 90-120 min storage at room temperature without rotation. Leucocytes were labelled by a proposed by the authors original method: to 10 ml heparinized blood 0,26-0,30 GB 99mTc sulphocolloid was added, incubated for 60 min; the free sulphocolloid was centrifuged in the syringe. The labelled cell sediment was suspended in physiological saline and re-injected. In a study of 16 patients on gamma camera, suspected of having inflammatory processes, the mean labelling effectiveness was 59%, similar to the one reported by other authors, who used similar technique and ready-made kits. Eight patients had positive finding, the inflammatory process in 7 being visualized as early as on hour 2 or 3 and in 1 on hour 24. The new method developed for specific leucocyte labelling with the use of Bulgarian kit may gain acceptance in the visualization of vague inflammatory processes. 3 figs., 4 refs

  18. Single molecule DNA detection with an atomic vapor notch filter

    Energy Technology Data Exchange (ETDEWEB)

    Uhland, Denis; Rendler, Torsten; Widmann, Matthias; Lee, Sang-Yun [University of Stuttgart and Stuttgart Research Center of Photonic Engineering (SCoPE) and IQST, 3rd Physics Institute, Stuttgart (Germany); Wrachtrup, Joerg; Gerhardt, Ilja [University of Stuttgart and Stuttgart Research Center of Photonic Engineering (SCoPE) and IQST, 3rd Physics Institute, Stuttgart (Germany); Max Planck Institute for Solid State Research, Stuttgart (Germany)

    2015-12-01

    The detection of single molecules has facilitated many advances in life- and material-science. Commonly the fluorescence of dye molecules is detected, which are attached to a non-fluorescent structure under study. For fluorescence microscopy one desires to maximize the detection efficiency together with an efficient suppression of undesired laser leakage. Here we present the use of the narrow-band filtering properties of hot atomic sodium vapor to selectively filter the excitation light from the red-shifted fluorescence of dye labeled single-stranded DNA molecules. A statistical analysis proves an enhancement in detection efficiency of more than 15% in a confocal and in a wide-field configuration. (orig.)

  19. Electronic Single Molecule Identification of Carbohydrate Isomers by Recognition Tunneling

    CERN Document Server

    Im, JongOne; Liu, Hao; Zhao, Yanan; Sen, Suman; Biswas, Sudipta; Ashcroft, Brian; Borges, Chad; Wang, Xu; Lindsay, Stuart; Zhang, Peiming

    2016-01-01

    Glycans play a central role as mediators in most biological processes, but their structures are complicated by isomerism. Epimers and anomers, regioisomers, and branched sequences contribute to a structural variability that dwarfs those of nucleic acids and proteins, challenging even the most sophisticated analytical tools, such as NMR and mass spectrometry. Here, we introduce an electron tunneling technique that is label-free and can identify carbohydrates at the single-molecule level, offering significant benefits over existing technology. It is capable of analyzing sub-picomole quantities of sample, counting the number of individual molecules in each subset in a population of coexisting isomers, and is quantitative over more than four orders of magnitude of concentration. It resolves epimers not well separated by ion-mobility and can be implemented on a silicon chip. It also provides a readout mechanism for direct single-molecule sequencing of linear oligosaccharides.

  20. 49 CFR 172.430 - POISON label.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false POISON label. 172.430 Section 172.430... SECURITY PLANS Labeling § 172.430 POISON label. (a) Except for size and color, the POISON label must be as follows: EC02MR91.029 (b) In addition to complying with § 172.407, the background on the POISON label...

  1. Nutrition Labeling Using a Computer Program

    Science.gov (United States)

    Metzger, Lloyd E.

    The 1990 Nutrition Labeling and Education Act mandated nutritional labeling of most foods. As a result, a large portion of food analysis is performed for nutritional labeling purposes. A food labeling guide and links to the complete nutritional labeling regulations are available online at http://vm.cfsan.fda.gov/˜dms/flg-toc.html. However, interpretation of these regulations and the appropriate usage of rounding rules, available nutrient content claims, reference amounts, and serving size can be difficult.

  2. IRMS detection of testosterone manipulated with 13C labeled standards in human urine by removing the labeled 13C

    International Nuclear Information System (INIS)

    Highlights: • 13C labeled testosterone can be used to adjust the isotope ratio of testosterone. • The novel testosterone cannot be detected by the regular IRMS method in doping test. • A method was explored to remove the labeled 13C. • The established method can be used to detect the manipulated testosterone. - Abstract: Isotope ratio mass spectrometry (IRMS) is applied to confirm testosterone (T) abuse by determining the carbon isotope ratios (δ13C value). However, 13C labeled standards can be used to control the δ13C value and produce manipulated T which cannot be detected by the current method. A method was explored to remove the 13C labeled atom at C-3 from the molecule of androsterone (Andro), the metabolite of T in urine, to produce the resultant (A-nor-5α-androstane-2,17-dione, ANAD). The difference in δ13C values between Andro and ANAD (Δδ13CAndro–ANAD, ‰) would change significantly in case manipulated T is abused. Twenty-one volunteers administered T manipulated with different 13C labeled standards. The collected urine samples were analyzed with the established method, and the maximum value of Δδ13CAndro–ANAD post ingestion ranged from 3.0‰ to 8.8‰. Based on the population reference, the cut-off value of Δδ13CAndro–ANAD for positive result was suggested as 1.2‰. The developed method could be used to detect T manipulated with 3-13C labeled standards

  3. Photochemistry of biological molecules

    International Nuclear Information System (INIS)

    Earlier studies of the photodamage induced by 254nm irradiation of linear alanine peptides in the solid state have been supplemented by an investigation into the gaseous photoproducts from the cyclic dipeptide, 3,6-dimethyl-2,5-diketopiperazine. The trans and cis isomers have been prepared and the photoproducts compared with those from the DL-mixture. The conformation of the molecule did influence the yield of gaseous products. CO was produced by peptide bond rupture with concomitant release of hydrogen. C02 was also produced. The use of N- and C-deuterated analogues together with relevant crystallographic and EPR data has enabled a detailed study of the mechanism of photodegradation to be made, from which it was concluded that the methyl protons are not inert but rather are the major source of the hydrogen observed on photolysis. (author)

  4. Forces in molecules.

    Science.gov (United States)

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W

    2007-01-01

    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another? PMID:17328425

  5. Lanthanide single molecule magnets

    CERN Document Server

    Tang, Jinkui

    2015-01-01

    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs, and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures – an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and...

  6. Lanthanide single molecule magnets

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jinkui; Zhang, Peng [Chinese Academy of Sciences, Changchun (China). Changchun Inst. of Applied Chemistry

    2015-10-01

    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures - an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and explore new directions.

  7. Phase sensitive spectral domain interferometry for label free biomolecular interaction analysis and biosensing applications

    Science.gov (United States)

    Chirvi, Sajal

    Biomolecular interaction analysis (BIA) plays vital role in wide variety of fields, which include biomedical research, pharmaceutical industry, medical diagnostics, and biotechnology industry. Study and quantification of interactions between natural biomolecules (proteins, enzymes, DNA) and artificially synthesized molecules (drugs) is routinely done using various labeled and label-free BIA techniques. Labeled BIA (Chemiluminescence, Fluorescence, Radioactive) techniques suffer from steric hindrance of labels on interaction site, difficulty of attaching labels to molecules, higher cost and time of assay development. Label free techniques with real time detection capabilities have demonstrated advantages over traditional labeled techniques. The gold standard for label free BIA is surface Plasmon resonance (SPR) that detects and quantifies the changes in refractive index of the ligand-analyte complex molecule with high sensitivity. Although SPR is a highly sensitive BIA technique, it requires custom-made sensor chips and is not well suited for highly multiplexed BIA required in high throughput applications. Moreover implementation of SPR on various biosensing platforms is limited. In this research work spectral domain phase sensitive interferometry (SD-PSI) has been developed for label-free BIA and biosensing applications to address limitations of SPR and other label free techniques. One distinct advantage of SD-PSI compared to other label-free techniques is that it does not require use of custom fabricated biosensor substrates. Laboratory grade, off-the-shelf glass or plastic substrates of suitable thickness with proper surface functionalization are used as biosensor chips. SD-PSI is tested on four separate BIA and biosensing platforms, which include multi-well plate, flow cell, fiber probe with integrated optics and fiber tip biosensor. Sensitivity of 33 ng/ml for anti-IgG is achieved using multi-well platform. Principle of coherence multiplexing for multi

  8. Positron emitter labeled enzyme inhibitors

    International Nuclear Information System (INIS)

    This invention involves a new strategy for imagining and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography

  9. Label-Enhanced Surface Plasmon Resonance: A New Concept for Improved Performance in Optical Biosensor Analysis

    Directory of Open Access Journals (Sweden)

    Niko Granqvist

    2013-11-01

    Full Text Available Surface plasmon resonance (SPR is a well-established optical biosensor technology with many proven applications in the study of molecular interactions as well as in surface and material science. SPR is usually applied in the label-free mode which may be advantageous in cases where the presence of a label may potentially interfere with the studied interactions per se. However, the fundamental challenges of label-free SPR in terms of limited sensitivity and specificity are well known. Here we present a new concept called label-enhanced SPR, which is based on utilizing strongly absorbing dye molecules in combination with the evaluation of the full shape of the SPR curve, whereby the sensitivity as well as the specificity of SPR is significantly improved. The performance of the new label-enhanced SPR method was demonstrated by two simple model assays: a small molecule assay and a DNA hybridization assay. The small molecule assay was used to demonstrate the sensitivity enhancement of the method, and how competitive assays can be used for relative affinity determination. The DNA assay was used to demonstrate the selectivity of the assay, and the capabilities in eliminating noise from bulk liquid composition variations.

  10. Synthesis and properties of fluorescent cotton cellulose labeled with norfloxacin

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    To expand the application of cellulose in the field of fluorescence techniques, the cotton cellulose was labeled with norfloxacin (Cell-NF) via a three-step reaction, involving alkali treatment, epoxy activation, and opening of the epoxy rings with norfloxacin molecules. And the coordination complexes of Cell-NF with rare earth ions terbium (Cell-NF-Tb) and europium (Cell-NF-Eu) were obtained. The products were detected by IR, TG, XPS, UV and fluorescence spectra. Results showed that the norfloxacin content of the labeled cellulose was about 6.73 w‰ and the start temperature of decomposition of the Cell-NF was raised by 40°C compared with the stock cotton cellulose. When excited at 340 nm, the Cell-NF, Cell-NF-Tb, and Cell-NF-Eu in the solid state could emit violet (430 nm), green (549 nm) and red (620 nm) light, respectively.

  11. Rhodamine B doped silica nanoparticle labels for protein microarray detection

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A core-shell Rhodamine B-doped SiO2 nanoparticle was synthesized and its fluorescent intensity was found to be 1000 times higher than that of individual Rhodamine B molecule. The doped nanoparticles were further conjugated with streptavidin and the resulting nanoparticles were used in the detection of reverse-phase protein microarrays, in which human IgG of various concentrations was first immobilized on aldehyde-modified glass slides and then biotinlyated goat anti human IgG as well as the labeled nanoparticles were sequentially conjugated. The calibration curve is linear over the range from 800 fg to 500 pg and the limit of detection is 100 fg, which is 8 times lower than that of streptavidin-labeled Cy3 fluorescent dyes. The dyedoped SiO2 nanoparticles show potentials for the protein array detection.

  12. Configuration spaces with summable labels

    OpenAIRE

    Salvatore, Paolo

    1999-01-01

    Let M be an n-manifold, and let A be a space with a partial sum behaving as an n-fold loop sum. We define the space C(M;A) of configurations in M with summable labels in A via operad theory. Some examples are symmetric products, labelled configuration spaces, and spaces of rational curves. We show that C(I^n,dI^n;A) is an n-fold delooping of C(I^n;A), and for n=1 it is the classifying space by Stasheff. If M is compact, parallelizable, and A is path connected, then C(M;A) is homotopic to the ...

  13. Denture labeling: A new approach

    Directory of Open Access Journals (Sweden)

    Pardeep K Bansal

    2011-01-01

    Full Text Available The need for denture labeling is important for forensic and social reasons in case patients need to be identified individually. The importance of denture marking has long been acknowledged by the dental profession. Over the years, various denture marking systems have been reported in the literature, but none till date fulfills all the prescribed ADA specifications. A simple, easy, inexpensive procedure for marking accurate identification marks on dentures with a lead foil is described here. The label caring the patient information is incorporated in the acrylic resin during the denture processing.

  14. In situ investigations of biological molecules using vibrational sum-frequency-generation spectroscopy

    OpenAIRE

    Howell, Caitlin

    2011-01-01

    The molecular-level understanding of biological molecules on solid surfaces is critical in areas including medicine, biologically-based industry, and the development of biotechnologies. In order to gain further knowledge of the orientation and organization of biological molecules adsorbed on surfaces, we used the label-free, interface-specific technique of sum-frequency generation (SFG) spectroscopy. This technique has the distinct advantage of being able to be operated in situ as well as ex ...

  15. Investigations on the uptake of 14C-labelled chlorhexidine diglutonate through dental enamel

    International Nuclear Information System (INIS)

    In this dissertation it was shown using radioactively labelled 14C tracer molecules that chlorhexidine is adsorbed on the dental surface of extracted teeth. Evidence for this was provided by the three following methods: a) back diffusion and release in rinses; b) thin layer chromatography of the adsorbed substance, and c) autoradiography. (orig./MG)

  16. The LB Films of Dansyl Chloride Labeled Octadecylamine and Its Fluorescence Lifetime

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Octadecylamine was derivatized with dansyl chloride (5-dimethylaminonaphthalene-1-sulfonyl chloride) in order to simplify and understand the LB films of fluorescent probe labeling proteins.Its monolayer and multilayers in the absence and presence of stearic acid were deposited by LB technique.Fluorescence spectra and lifetimes of the fluorescent products were studied to elucidate the microenvironment of molecules in the LB films.

  17. Connected Component Labeling Using Components Neighbors-Scan Labeling Approach

    Directory of Open Access Journals (Sweden)

    Akmal Rakhmadi

    2010-01-01

    Full Text Available Problem statement: Many approaches have been proposed in previous such as the classic sequential connected components labeling algorithm which is relies on two subsequent raster-scans of a binary image. This method produced good performance in terms of accuracy, but because of the implementation of the image processing systems now requires faster process of the computer, the speed of this technique’s process has become an important issue. Approach: A computational approach, called components neighbors-scan labeling algorithm for connected component labeling was presented in this study. This algorithm required scanning through an image only once to label connected components. The algorithm started by scanning from the head of the component’s group, before tracing all the components neighbors by using the main component’s information. This algorithm had desirable characteristics, it is simple while promoted accuracy and low time consuming. By using a table of components, this approach also gave other advantages as the information for the next higher process. Results: The approach had been tested with a collection of binary images. In practically all cases, the technique had successfully given the desired result. Averagely, from the results the algorithm increased the speed around 67.4% from the two times scanning method. Conclusion: Conclusion from the comparison with the previous method, the approach of components neighbors-scan for connected component labeling promoted speed, accuracy and simplicity. The results showed that the approach has a good performance in terms of accuracy, the time consumed and the simplicity of the algorithm.

  18. Fluorine-18 labeled tracers for PET studies in the neurosciences

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yu-Shin; Fowler, J.S.

    1995-12-31

    This chapter focuses on fluorine-18, the positron emitter with the longest half-life, the lowest positron energy and probably, the most challenging chemistry. The incorporation of F-18 into organic compounds presents many challenges, including: the need to synthesize and purify the compound within a 2--3 hour time frame; the limited number of labeled precursor molecules; the need to work on a microscale; and the need to produce radiotracers which are chemically and radiochemically pure, sterile and pyrogen-free, and suitable for intravenous injection. The PET method and F-18 labeling of organic molecules are described followed by highlights of the applications of F-18 labeled compounds in the neurosciences and neuropharmacology. It is important to emphasize the essential and pivotal role that organic synthesis has played in the progression of the PET field over the past twenty years from one in which only a handful of institutions possessed the instrumentation and staff to carry out research to the present-day situation where there are more than 200 PET centers worldwide. During this period PET has become an important scientific tool in the neurosciences, cardiology and oncology. It is important to point out that PET is by no means a mature field. The fact that a hundreds of different F-18 labeled compounds have been developed but only a few possess the necessary selectivity and sensitivity in vivo to track a specific biochemical process illustrates this and underscores a major difficulty in radiotracer development, namely the selection of priority structures for synthesis and the complexities of the interactions between chemical compounds and living systems. New developments in rapid organic synthesis are needed in order to investigate new molecular targets and to improve the quantitative nature of PET experiments.

  19. Fluorine-18 labeled tracers for PET studies in the neurosciences

    International Nuclear Information System (INIS)

    This chapter focuses on fluorine-18, the positron emitter with the longest half-life, the lowest positron energy and probably, the most challenging chemistry. The incorporation of F-18 into organic compounds presents many challenges, including: the need to synthesize and purify the compound within a 2--3 hour time frame; the limited number of labeled precursor molecules; the need to work on a microscale; and the need to produce radiotracers which are chemically and radiochemically pure, sterile and pyrogen-free, and suitable for intravenous injection. The PET method and F-18 labeling of organic molecules are described followed by highlights of the applications of F-18 labeled compounds in the neurosciences and neuropharmacology. It is important to emphasize the essential and pivotal role that organic synthesis has played in the progression of the PET field over the past twenty years from one in which only a handful of institutions possessed the instrumentation and staff to carry out research to the present-day situation where there are more than 200 PET centers worldwide. During this period PET has become an important scientific tool in the neurosciences, cardiology and oncology. It is important to point out that PET is by no means a mature field. The fact that a hundreds of different F-18 labeled compounds have been developed but only a few possess the necessary selectivity and sensitivity in vivo to track a specific biochemical process illustrates this and underscores a major difficulty in radiotracer development, namely the selection of priority structures for synthesis and the complexities of the interactions between chemical compounds and living systems. New developments in rapid organic synthesis are needed in order to investigate new molecular targets and to improve the quantitative nature of PET experiments

  20. The radio-labeling of Ciprofloxacin with Technetium-99m

    International Nuclear Information System (INIS)

    Even with rapid technological development in the field of diagnostic imaging, the localization of infection continues to pose challenges in day-to-day routine clinical practice. Tc-99m Ciprofloxacin is a relatively new radiopharmaceutical, which has proven its utility in imaging infection. This paper presents a new method of labeling Ciprofloxacin with Tc-99m using SnCI2.2H20 as reducing agent. The procedure used 2 mg of Ciprofloxacin manufactured by Bayer, 400 μg of SnCI2.2H20 (Sigma Chemical Co.) and 185MBq of Technetium-99m in the form of pertechnetate (Tc-99mO4) in a volume of 300 μl. The labeling was carried out at 100 deg. C for 10 minutes and at ambient temperature for a similar period of time. The solution obtained was filtered using millipore filter of 0.22 μm size. The efficiency of the labeling, verified by ascending chromatography on Whatman No.1 paper was found to be 97.3 % (±1.6), while it was 96.8% (±2.3) using Whatman No.3 paper and 96.6% (± 2.1) using thin-layer chromatography. Chromatography by exclusion chromatography (Bio-Gel P 10) was used for confirmation of the above results. The labeled molecules were eluted first, followed by the molecules of Technetium-99m while the colloids remained attached to the column. The results of the present study are comparable with the results of previous studies reported in literature. (author)

  1. Pharmacogenomic Biomarkers: an FDA Perspective on Utilization in Biological Product Labeling.

    Science.gov (United States)

    Schuck, Robert N; Grillo, Joseph A

    2016-05-01

    Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharmacogenomics is a key component of precision medicine and can be utilized to select optimal doses for patients, more precisely identify individuals who will respond to a treatment and avoid serious drug-related toxicities. Since pharmacogenomic biomarker information can help inform drug dosing, efficacy, and safety, pharmacogenomic data are critically reviewed by FDA staff to ensure effective use of pharmacogenomic strategies in drug development and appropriate incorporation into product labels. Pharmacogenomic information may be provided in drug or biological product labeling to inform health care providers about the impact of genotype on response to a drug through description of relevant genomic markers, functional effects of genomic variants, dosing recommendations based on genotype, and other applicable genomic information. The format and content of labeling for biologic drugs will generally follow that of small molecule drugs; however, there are notable differences in pharmacogenomic information that might be considered useful for biologic drugs in comparison to small molecule drugs. Furthermore, the rapid entry of biologic drugs for treatment of rare genetic diseases and molecularly defined subsets of common diseases will likely lead to increased use of pharmacogenomic information in biologic drug labels in the near future. In this review, we outline the general principles of therapeutic product labeling and discuss the utilization of pharmacogenomic information in biologic drug labels. PMID:26912182

  2. Third party labeling and the consumer decision process: the case of the PGI European label

    OpenAIRE

    Larceneux, Fabrice; Carpenter, Marie

    2008-01-01

    The objective of this research is to explore the decision-making process of consumers when faced with food products that have values-based labels. An experimental methodology was used to test the impact of a label of origin guaranteed by the European Union, the Protected Geographic Indications (PGI) label. Consumers' reactions to two different products were investigated with four different presentations: without a specific label, with a simple regional label, with both a regional label and th...

  3. Calcium phosphate nanoparticles as versatile carrier for small and large molecules across cell membranes

    International Nuclear Information System (INIS)

    The successful transport of molecules across the cell membrane is a key point in biology and medicine. In most cases, molecules alone cannot penetrate the cell membrane, therefore an efficient carrier is needed. Calcium phosphate nanoparticles (diameter: 100–250 nm, depending on the functionalization) were loaded with fluorescent oligonucleotides, peptide, proteins, antibodies, polymers or porphyrins and characterized by dynamic light scattering, nanoparticle tracking analysis and scanning electron microscopy. Any excess of molecules was removed by ultracentrifugation, and the dissolved molecules at the same concentration were used as control. The uptake of such fluorescence-labeled nanoparticles into HeLa cells was monitored by fluorescence microscopy and confocal laser scanning microscopy. Calcium phosphate nanoparticles were able to transport all molecules across the cell membrane, whereas the dissolved molecules alone were taken up only to a very small extent or even not at all.

  4. Nutrition Marketing on Food Labels

    Science.gov (United States)

    Nutrition marketing may influence purchasing behavior and thereby be a factor in the obesity epidemic. Very little peer-reviewed research has been published which investigates the relationship between nutrition marketing on food labels and consumer behavior. The purpose of this paper was to give an ...

  5. Improving the energy labelling scheme

    DEFF Research Database (Denmark)

    Gram-Hanssen, Kirsten; Christensen, Toke Haunstrup

    This report summarises the main results of an EU project on consumer response to energy labels in buildings. This report is mainly directed at Danish policy makers. The main focus is therefore on results that are relevant from a Danish point of view and on how they can be used to further strength...

  6. Reactions of oriented molecules.

    Science.gov (United States)

    Brooks, P R

    1976-07-01

    Beams of oriented molecules have been used to directly study geometrical requirements in chemical reactions. These studies have shown that reactivity is much greater in some orientations than others and demonstrated the existence of steric effects. For some reactions portions of the orientation results are in good accord with traditional views of steric hindrance, but for others it is clear that our chemical intuition needs recalibrating. Indeed, the information gained from simultaneously orienting the reactants and observing the scattering angle of the products may lead to new insights about the detailed mechanism of certain reactions. Further work must be done to extend the scope and detail of the studies described here. More detailed information is needed on the CH(3)I reaction and the CF(3)I reaction. The effects of alkyl groups of various sizes and alkali metals of various sizes are of interest. In addition, reactions where a long-lived complex is formed should be studied to see if orientation is important. Finally, it would be of interest to apply the technique to the sort of reactions that led to our interest in the first place: the S(N)2 displacements in alkyl halides where the fascinating Walden inversion occurs. PMID:17793988

  7. Molecule-based magnets

    Indian Academy of Sciences (India)

    J V Yakhmi

    2009-06-01

    The conventional magnetic materials used in current technology, such as, Fe, Fe2O3, Cr2O3, SmCo5, Nd2Fe14B etc are all atom-based, and their preparation/processing require high temperature routes. Employing self-assembly methods, it is possible to engineer a bulk molecular material with long-range magnetic order, mainly because one can play with the weak intermolecular interactions. Since the first successful synthesis of molecular magnets in 1986, a large variety of them have been synthesized, which can be categorized on the basis of the chemical nature of the magnetic units involved: organic-, metal-based systems, heterobimetallic assemblies, or mixed organic–inorganic systems. The design of molecule-based magnets has also been extended to the design of poly-functional molecular magnets, such as those exhibiting second-order optical nonlinearity, liquid crystallinity, or chirality simultaneously with long-range magnetic order. Solubility, low density and biocompatibility are attractive features of molecular magnets. Being weakly coloured, unlike their opaque classical magnet ‘cousins’ listed above, possibilities of photomagnetic switching exist. Persistent efforts also continue to design the ever-elusive polymer magnets towards applications in industry. While providing a brief overview of the field of molecular magnetism, this article highlights some recent developments in it, with emphasis on a few studies from the author’s own lab.

  8. Tunnelling of a molecule

    International Nuclear Information System (INIS)

    A quantum-mechanical description of tunnelling is presented for a one-dimensional system with internal oscillator degrees of freedom. The 'charged diatomic molecule' is frustrated on encountering a barrier potential by its centre of charge not being coincident with its centre of mass, resulting in transitions amongst internal states. In an adiabatic limit, the tunnelling of semiclassical coherent-like oscillator states is shown to exhibit the Hartman and Bueuttiker-Landauer times tH and tBL, with the time dependence of the coherent state parameter for the tunnelled state given by α(t) = α e-iω(t+Δt) , Δt = tH - itBL. A perturbation formalism is developed, whereby the exact transfer matrix can be expanded to any desired accuracy in a suitable limit. An 'intrinsic' time, based on the oscillator transition rate during tunnelling, transmission or reflection, is introduced. In simple situations the resulting intrinsic tunnelling time is shown to vanish to lowest order. In the general case a particular (nonzero) parametrisation is inferred, and its properties discussed in comparison with the literature on tunnelling times for both wavepackets and internal clocks. Copyright (1998) CSIRO Australia

  9. Organic Molecules in Meteorites

    Science.gov (United States)

    Martins, Zita

    2015-08-01

    Carbonaceous meteorites are primitive samples from the asteroid belt, containing 3-5wt% organic carbon. The exogenous delivery of organic matter by carbonaceous meteorites may have contributed to the organic inventory of the early Earth. The majority (>70%) of the meteoritic organic material consist of insoluble organic matter (IOM) [1]. The remaining meteoritic organic material (Haber-Bosch type gas-grain reactions after the meteorite parent body cooled to lower temperatures [13, 14].The analysis of the abundances and distribution of the organic molecules present in meteorites helps to determine the physical and chemical conditions of the early solar system, and the prebiotic organic compounds available on the early Earth.[1] Cody and Alexander (2005) GCA 69, 1085. [2] Cronin and Chang (1993) in: The Chemistry of Life’s Origin. pp. 209-258. [3] Martins and Sephton (2009) in: Amino acids, peptides and proteins in organic chemistry. pp. 1-42. [4] Martins (2011) Elements 7, 35. [5] Botta et al. (2007) MAPS 42, 81. [6] Martins et al. (2015) MAPS, in press. [7] Cooper and Cronin (1995) GCA 59, 1003. [8] Glavin et al. (2006) MAPS. 41, 889. [9] Glavin et al. (2011) MAPS 45, 1948. [10] Elsila et al. (2005) GCA 5, 1349. [11] Glavin and Dworkin (2009) PNAS 106, 5487. [12] Pizzarello et al. (2003) GCA 67, 1589. [13] Chan et al. (2012) MAPS. 47, 1502. [14] Burton et al. (2011) MAPS 46, 1703.

  10. Thread bonds in molecules

    CERN Document Server

    Ivlev, B

    2015-01-01

    Unusual chemical bonds are proposed. Each bond is almost covalent but is characterized by the thread of a small radius $\\sim 0.6\\times 10^{-11}$cm, between two nuclei in a molecule. The main electron density is concentrated outside the thread as in a covalent bond. The thread is formed by the electron wave function which has a tendency to be singular on it. The singularity along the thread is cut off by electron "vibrations" due to the interaction with zero point electromagnetic oscillations. The electron energy has its typical value of (1-10)eV. Due to the small tread radius the uncertainty of the electron momentum inside the thread is large resulting in a large electron kinetic energy $\\sim 1 MeV$. This energy is compensated by formation of a potential well due to the reduction of the energy of electromagnetic zero point oscillations. This is similar to formation of a negative van der Waals potential. Thread bonds are stable and cannot be created or destructed in chemical or optical processes.

  11. Strongly interacting ultracold polar molecules

    Science.gov (United States)

    Gadway, Bryce; Yan, Bo

    2016-08-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole–dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  12. Strongly interacting ultracold polar molecules

    CERN Document Server

    Gadway, Bryce

    2016-01-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole-dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  13. Molecules Best Paper Award 2012

    Directory of Open Access Journals (Sweden)

    Derek J. McPhee

    2012-02-01

    Full Text Available Molecules starts to institute the “Best Paper” award to recognize these outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the first “Molecules Best Paper Award” for 2012. Nominations were selected by the editor-in-chief and selected editorial board members from all the papers published in 2008. [...

  14. Molecules Best Paper Award 2014

    Directory of Open Access Journals (Sweden)

    Derek J. McPhee

    2014-01-01

    Full Text Available Molecules instituted some years ago a “Best Paper” award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published each year in Molecules. We are pleased to announce the third “Molecules Best Paper Award” for 2014. The winners were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2010. Reviews and research papers were evaluated separately.

  15. Molecules Best Paper Award 2013

    Directory of Open Access Journals (Sweden)

    Derek J. McPhee

    2013-02-01

    Full Text Available Molecules has started to institute a "Best Paper" award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the second "Molecules Best Paper Award" for 2013. Candidates were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2009.

  16. Recoiling DNA Molecule: Simulation & Experiment

    OpenAIRE

    Neto, Jose Coelho; Dickman, Ronald; Mesquita, O. N.

    2002-01-01

    Single molecule DNA experiments often generate data from force versus extension measurements involving the tethering of a microsphere to one end of a single DNA molecule while the other is attached to a substrate. We show that the persistence length of single DNA molecules can also be measured based on the recoil dynamics of these DNA-microsphere complexes if appropriate corrections are made to the friction coefficient of the microsphere in the vicinity of the substrate. Comparison between co...

  17. The migration of synthetic magnetic nanoparticle labeled dendritic cells into lymph nodes with optical imaging

    Directory of Open Access Journals (Sweden)

    Su H

    2013-10-01

    Full Text Available Hang Su,1,* Yongbin Mou,1,* Yanli An,2 Wei Han,1 Xiaofeng Huang,1 Guohua Xia,3 Yanhong Ni,1 Yu Zhang,4 Jianmin Ma,1 Qingang Hu1,5 1Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China; 2Jiangsu Key Lab of Molecular and Function Imaging, Department of Radiology; 3Department of Hematology, Zhongda Hospital, Medical School, 4State Key Laboratory of Molecule and Bimolecular Electronics, Jiangsu Provincial Laboratory for Biomaterials and Devices; Southeast University, Nanjing, People's Republic of China; 5Leeds Dental Institute, Faculty of Medicine and health, University of Leeds, Leeds, United Kingdom*These authors contributed equally to this workBackground: The successful biotherapy of carcinoma with dendritic cell (DC vaccines pivotally relies on DCs’ migratory capability into lymph tissues and activation of T cells. Accurate imaging and evaluation of DC migration in vivo have great significance during antitumor treatment with DC vaccine. We herein examined the behavior of DCs influenced by synthetic superparamagnetic iron oxide (SPIO nanoparticle labeling.Methods: γ-Fe2O3 nanoparticles were prepared and DCs, which were induced from bone marrow monocytes of enhanced green fluorescent protein (EGFP transgenic mice, were labeled. The endocytosis of the SPIO, surface molecules, cell apoptosis and fluorescence intensity of EGFP-DCs were displayed by Prussian blue staining and flow cytometry (FCM, respectively. After EGFP-DCs, labeled with SPIO, were injected into footpads (n = 5 for 24 hours, the mice were examined in vivo by optical imaging (OPI. Meanwhile, confocal imaging and FCM were applied, respectively, to detect the migration of labeled DCs into draining lymph nodes.Results: Nearly 100% of cells were labeled by the SPIO, in which the intracellular blue color gradually deepened and the iron contents rose with the increase of labeling iron concentrations

  18. STM investigation of surfactant molecules

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Adsorption and self-organization of sodium alkyl sulfonates (STS and SHS) have been studied on HOPG by using the in situ scanning tunneling microscopy (STM). Both SHS and STS molecules adsorb on the HOPG surface and form long-range well-ordered monolayers. The neighboring molecules in different rows form a "head to head" configuration. In the high-resolution images of STS and SHS molecules, one end of the molecules shows bright spots which are attributed to the SO3- groups.

  19. Molecules Best Paper Award 2015

    Directory of Open Access Journals (Sweden)

    Derek J. McPhee

    2015-01-01

    Full Text Available Molecules instituted some years ago a “Best Paper” award to recognize the most outstanding papers in the area of organic synthesis, natural products, medicinal chemistry and molecular diversity published each year in Molecules. We are pleased to announce the third “Molecules Best Paper Award” for 2015. The winners were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2011. Reviews and research papers were evaluated separately. We are pleased to announce that the following eight papers have won the Molecules Best Paper Award for 2015:[...

  20. Aromatic molecules as spintronic devices

    International Nuclear Information System (INIS)

    In this paper, we study the spin-dependent electron transport through aromatic molecular chains attached to two semi-infinite leads. We model this system taking into account different geometrical configurations which are all characterized by a tight binding Hamiltonian. Based on the Green's function approach with a Landauer formalism, we find spin-dependent transport in short aromatic molecules by applying external magnetic fields. Additionally, we find that the magnetoresistance of aromatic molecules can reach different values, which are dependent on the variations in the applied magnetic field, length of the molecules, and the interactions between the contacts and the aromatic molecule

  1. The labeling debate in the United States.

    Science.gov (United States)

    Marchant, Gary E; Cardineau, Guy A

    2013-01-01

    The mandatory labeling of genetically modified (GM) food has become the predominant policy issue concerning biotechnology in the United States. The controversy over GM labeling is being debated at several different levels and branches of government. At the federal level, the Food and Drug Administration, which has primary jurisdiction over food safety and labeling, has steadfastly refused to require labeling of GM foods since 1992 based on its conclusion that GM foods as a category present no unique or higher risks than other foods. Proposed legislation has been repeatedly introduced in the US. Congress over the years to mandate GM labeling, but has made very little progress. With federal labeling requirements apparently stalled, the main activity has switched to the state level, where numerous individual states are considering mandatory GM labeling, either through legislation or proposition. The debate over GM labeling, at both the federal and state levels, has focused on five issues: (1) public opinion; (2) the legality of labeling requirements; (3) the risks and benefits of GM foods; (4) the costs and burdens of GM labeling; and (5) consumer choice. While the pro-labeling forces argue that all of these factors weigh in favor of mandatory GM labeling, a more careful evaluation of the evidence finds that all five factors weigh decisively against mandatory GM labeling requirements. PMID:23982076

  2. Label-free probing of genes by time-domain terahertz sensing

    International Nuclear Information System (INIS)

    A label-free sensing approach for the label-free characterization of genetic material with terahertz (THz) electromagnetic waves is presented. Time-resolved THz analysis of polynucleotides demonstrates a strong dependence of the complex refractive index of DNA molecules in the THz frequency range on their hybridization state. By monitoring THz signals one can thus infer the binding state (hybridized or denatured) of oligo- and polynucleotides, enabling the label-free determination the genetic composition of unknown DNA sequences. A broadband experimental proof-of-principle in a free-space analytic configuration, as well as a higher-sensitivity approach using integrated THz sensors reaching femtomol detection levels and demonstrating the capability to detect single-base mutations, are presented. The potential application for next generation high-throughput label-free genetic analytic systems is discussed

  3. Label-free probing of genes by time-domain terahertz sensing

    Energy Technology Data Exchange (ETDEWEB)

    Bolivar, P Haring [Institut fuer Halbleitertechnik, RWTH Aachen, Sommerfeldstr. 24, D-52056 Aachen (Germany); Brucherseifer, M [Institut fuer Halbleitertechnik, RWTH Aachen, Sommerfeldstr. 24, D-52056 Aachen (Germany); Nagel, M [Institut fuer Halbleitertechnik, RWTH Aachen, Sommerfeldstr. 24, D-52056 Aachen (Germany); Kurz, H [Institut fuer Halbleitertechnik, RWTH Aachen, Sommerfeldstr. 24, D-52056 Aachen (Germany); Bosserhoff, A [Institut fuer Pathologie, Universitaet Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg (Germany); Buettner, R [Institut fuer Pathologie, Universitaetsklinikum Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn (Germany)

    2002-11-07

    A label-free sensing approach for the label-free characterization of genetic material with terahertz (THz) electromagnetic waves is presented. Time-resolved THz analysis of polynucleotides demonstrates a strong dependence of the complex refractive index of DNA molecules in the THz frequency range on their hybridization state. By monitoring THz signals one can thus infer the binding state (hybridized or denatured) of oligo- and polynucleotides, enabling the label-free determination the genetic composition of unknown DNA sequences. A broadband experimental proof-of-principle in a free-space analytic configuration, as well as a higher-sensitivity approach using integrated THz sensors reaching femtomol detection levels and demonstrating the capability to detect single-base mutations, are presented. The potential application for next generation high-throughput label-free genetic analytic systems is discussed.

  4. Single-target molecule detection with nonbleaching multicolor optical immunolabels

    Science.gov (United States)

    Schultz, Sheldon; Smith, David R.; Mock, Jack J.; Schultz, David A.

    2000-02-01

    We introduce and demonstrate the use of colloidal silver plasmon-resonant particles (PRPs) as optical reporters in typical biological assays. PRPs are ultrabright, nanosized optical scatterers, which scatter light elastically and can be prepared with a scattering peak at any color in the visible spectrum. PRPs are readily observed individually with a microscope configured for dark-field microscopy, with white-light illumination of typical power. Here we illustrate the use of PRPs, surface coated with standard ligands, as target-specific labels in an in situ hybridization and an immunocytology assay. We propose that PRPs can replace or complement established labels, such as those based on radioactivity, fluorescence, chemiluminescence, or enzymatic/colorimetric detection that are used routinely in biochemistry, cell biology, and medical diagnostic applications. Moreover, because PRP labels are nonbleaching and bright enough to be rapidly identified and counted, an ultrasensitive assay format based on single-target molecule detection is now practical. We also present the results of a model sandwich immunoassay for goat anti-biotin antibody, in which the number of PRP labels counted in an image constitutes the measured signal.

  5. A Chemical Probe that Labels Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Nao Hirata

    2014-03-01

    Full Text Available A small-molecule fluorescent probe specific for human pluripotent stem cells would serve as a useful tool for basic cell biology research and stem cell therapy. Screening of fluorescent chemical libraries with human induced pluripotent stem cells (iPSCs and subsequent evaluation of hit molecules identified a fluorescent compound (Kyoto probe 1 [KP-1] that selectively labels human pluripotent stem cells. Our analyses indicated that the selectivity results primarily from a distinct expression pattern of ABC transporters in human pluripotent stem cells and from the transporter selectivity of KP-1. Expression of ABCB1 (MDR1 and ABCG2 (BCRP, both of which cause the efflux of KP-1, is repressed in human pluripotent stem cells. Although KP-1, like other pluripotent markers, is not absolutely specific for pluripotent stem cells, the identified chemical probe may be used in conjunction with other reagents.

  6. A Multi-Label Classification Approach Based on Correlations Among Labels

    Directory of Open Access Journals (Sweden)

    Raed Alazaidah

    2015-02-01

    Full Text Available Multi label classification is concerned with learning from a set of instances that are associated with a set of labels, that is, an instance could be associated with multiple labels at the same time. This task occurs frequently in application areas like text categorization, multimedia classification, bioinformatics, protein function classification and semantic scene classification. Current multi-label classification methods could be divided into two categories. The first is called problem transformation methods, which transform multi-label classification problem into single label classification problem, and then apply any single label classifier to solve the problem. The second category is called algorithm adaptation methods, which adapt an existing single label classification algorithm to handle multi-label data. In this paper, we propose a multi-label classification approach based on correlations among labels that use both problem transformation methods and algorithm adaptation methods. The approach begins with transforming multi-label dataset into a single label dataset using least frequent label criteria, and then applies the PART algorithm on the transformed dataset. The output of the approach is multi-labels rules. The approach also tries to get benefit from positive correlations among labels using predictive Apriori algorithm. The proposed approach has been evaluated using two multi-label datasets named (Emotions and Yeast and three evaluation measures (Accuracy, Hamming Loss, and Harmonic Mean. The experiments showed that the proposed approach has a fair accuracy in comparison to other related methods.

  7. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... Cerebral Palsy: Caring for Your Child All About Food Allergies How to Read a Nutrition Facts Label ( ... THIS TOPIC Keeping Portions Under Control Figuring Out Food Labels Healthy Food Shopping If My Child Has ...

  8. Preparation of 35S labelled thiosemicarbazone

    International Nuclear Information System (INIS)

    A 35S labelled thiosemicarbazone is prepared, on a millimole scale by reacting labelled thiocyanate with hydrazine sulfate in ethanolic medium. The hydrazine thiocyanate so formed is then condensed with aldehyde to form the thiosemicarbazone

  9. Preparation of methyl-3H labelled dimethylnitrosamine

    International Nuclear Information System (INIS)

    Tritium labelled dimethylamine was prepared from benzalmethylimine in reaction with methyl-3H iodide followed by hydrolysis. The product was converted with sodium nitrite in glacial acetic acid into labelled dimethylnitrosamine. The radiochemical yield was 85%. (author)

  10. Labelling schemes: From a consumer perspective

    DEFF Research Database (Denmark)

    Juhl, Hans Jørn; Stacey, Julia

    2000-01-01

    , their size etc. are studied before setting up a label scheme. A new labelling study was launched in 2000, the purpose of which is to: * improve the foundation for evaluating the value and effect of labelling schemes * improve the possibilities for pursuing an active consumer policy within the area * give......Labelling of food products attracts a lot of political attention these days. As a result of a number of food scandals, most European countries have acknowledged the need for more information and better protection of consumers. Labelling schemes are one way of informing and guiding consumers....... However, initiatives in relation to labelling schemes seldom take their point of departure in consumers' needs and expectations; and in many cases, the schemes are defined by the institutions guaranteeing the label. It is therefore interesting to study how consumers actually value labelling schemes...

  11. Ivabradine: A Review of Labeled and Off-Label Uses.

    Science.gov (United States)

    Oliphant, Carrie S; Owens, Ryan E; Bolorunduro, Oluwaseyi B; Jha, Sunil K

    2016-10-01

    Ivabradine is a unique medication recently approved in the USA for the treatment of select heart failure patients. It was first approved for use in several countries around the world over a decade ago as an anti-anginal agent, with subsequent approval for use in heart failure patients. Since ivabradine has selective activity blocking the I f currents in the sinus node, it can reduce heart rate without appreciable effects on blood pressure. Given this heart-rate-specific effect, it has been investigated in many off-label indications as an alternative to traditional heart-rate-reducing medications such as beta blockers and calcium channel blockers. We conducted searches of PubMed and Google Scholar for ivabradine, heart failure, HFrEF, HFpEF, angina, coronary artery disease, inappropriate sinus tachycardia, postural orthostatic hypotension, coronary computed tomography angiography and atrial fibrillation. We reviewed and included studies, case reports, and case series published between 1980 and June 2016 if they provided information relevant to the practicing clinician. In many cases, larger clinical trials are needed to solidify the benefit of ivabradine, although studies indicate benefit in most therapeutic areas explored to date. The purpose of this paper is to review the current labeled and off-label uses of ivabradine, with a focus on clinical trial data. PMID:27405864

  12. Fluorescence enhancement of single DNA molecules confined in Si/SiO2 nanochannels

    DEFF Research Database (Denmark)

    Westerlund, F.; Persson, Karl Fredrik; Kristensen, Anders;

    2010-01-01

    We demonstrate that the detected emission intensity from YOYO-labeled DNA molecules confined in 180 nm deep Si/SiO2 nano-funnels changes significantly and not monotonically with the width of the funnel. This effect may be of importance for quantitative fluorescence microscopy and for experiments...

  13. Consistent assignment of the vibrations of symmetric and asymmetric para-disubstituted benzene molecules

    Science.gov (United States)

    Andrejeva, Anna; Gardner, Adrian M.; Tuttle, William D.; Wright, Timothy G.

    2016-03-01

    We give a description of the phenyl-ring-localized vibrational modes of the ground states of the para-disubstituted benzene molecules including both symmetric and asymmetric cases. In line with others, we quickly conclude that the use of Wilson mode labels is misleading and ambiguous; we conclude the same regarding the related ones of Varsányi. Instead we label the modes consistently based upon the Mulliken (Herzberg) method for the modes of para-difluorobenzene (pDFB). Since we wish the labelling scheme to cover both symmetrically- and asymmetrically-substituted molecules, we apply the Mulliken labelling under C2v symmetry. By studying the variation of the vibrational wavenumbers with mass of the substituent, we are able to identify the corresponding modes across a wide range of molecules and hence provide consistent assignments. Particularly interesting are pairs of vibrations that evolve from in- and out-of-phase motions in pDFB to more localized modes in asymmetric molecules. We consider the para isomers of the following: the symmetric dihalobenzenes, xylene, hydroquinone, the asymmetric dihalobenzenes, halotoluenes, halophenols and cresol.

  14. Single-molecule imaging of hyaluronan in human synovial fluid

    Science.gov (United States)

    Kappler, Joachim; Kaminski, Tim P.; Gieselmann, Volkmar; Kubitscheck, Ulrich; Jerosch, Jörg

    2010-11-01

    Human synovial fluid contains a high concentration of hyaluronan, a high molecular weight glycosaminoglycan that provides viscoelasticity and contributes to joint lubrication. In osteoarthritis synovial fluid, the concentration and molecular weight of hyaluronan decrease, thus impairing shock absorption and lubrication. Consistently, substitution of hyaluronan (viscosupplementation) is a widely used treatment for osteoarthritis. So far, the organization and dynamics of hyaluronan in native human synovial fluid and its action mechanism in viscosupplementation are poorly characterized at the molecular level. Here, we introduce highly sensitive single molecule microscopy to analyze the conformation and interactions of fluorescently labeled hyaluronan molecules in native human synovial fluid. Our findings are consistent with a random coil conformation of hyaluronan in human synovial fluid, and point to specific interactions of hyaluronan molecules with the synovial fluid matrix. Furthermore, single molecule microscopy is capable of detecting the breakdown of the synovial fluid matrix in osteoarthritis. Thus, single molecule microscopy is a useful new method to probe the structure of human synovial fluid and its changes in disease states like osteoarthritis.

  15. 77 FR 12313 - Food Labeling Workshop; Public Workshop

    Science.gov (United States)

    2012-02-29

    ..., (3) nutrition labeling requirements, (4) health and nutrition claims, and (5) special labeling issues... with labeling requirements, especially in light of growing concerns about obesity and food...

  16. Do Consumers Really Use Food Labels?

    OpenAIRE

    Ward, Ronald W.; Jauregui, Carlos E.

    2006-01-01

    Ordered Probit models are used to estimate the probabilities of consumers reading food labels for harmful ingredients and for using labels to assist with food purchasing decisions. Demographics, health concerns, attitudes, and eating habits are shown to influence the likelihood of using food labels. Effects from over 25 variables are ranked in terms of their relative impacts on the use of food labels. Dieting, concerns about calories, foreign foods, and many other variable effects on the use ...

  17. Interferometric scattering microscopy and its combination with single-molecule fluorescence imaging.

    Science.gov (United States)

    Ortega Arroyo, Jaime; Cole, Daniel; Kukura, Philipp

    2016-04-01

    Interferometric scattering microscopy (iSCAT) is a light scattering-based imaging modality that offers a unique combination of imaging speed and precision for tracking nanoscopic labels and enables label-free optical sensing down to the single-molecule level. In contrast to fluorescence, iSCAT does not suffer from limitations associated with dye photochemistry and photophysics, or the requirement for fluorescent labeling. Here we present a protocol for constructing an iSCAT microscope from commercially available optical components and demonstrate its compatibility with simultaneously operating single-molecule, objective-type, total internal reflection fluorescence microscopy. Given an intermediate level of experience with optics and microscopy, for instance graduate-level familiarity with laser beam steering and optical components, this protocol can be completed in a time frame of 2 weeks. PMID:26938114

  18. Single-molecule magnet engineering

    DEFF Research Database (Denmark)

    Pedersen, Kasper Steen; Bendix, Jesper; Clérac, Rodolphe

    2014-01-01

    to delicately tune, for instance, the properties of molecules that behave as "magnets", the so-called single-molecule magnets (SMMs). Although many interesting SMMs have been prepared by a more or less serendipitous approach, the assembly of predesigned, isolatable molecular entities into higher nuclearity...

  19. Elemental labelling combined with liquid chromatography inductively coupled plasma mass spectrometry for quantification of biomolecules: A review

    OpenAIRE

    Kretschy, Daniela; Koellensperger, Gunda; Hann, Stephan

    2012-01-01

    This article reviews novel quantification concepts where elemental labelling is combined with flow injection inductively coupled plasma mass spectrometry (FI-ICP-MS) or liquid chromatography inductively coupled plasma mass spectrometry (LC–ICP-MS), and employed for quantification of biomolecules such as proteins, peptides and related molecules in challenging sample matrices. In the first sections an overview on general aspects of biomolecule quantification, as well as of labelling will be pre...

  20. Alternating Laser Excitation for Solution-Based Single-Molecule FRET.

    Science.gov (United States)

    Kapanidis, Achillefs; Majumdar, Devdoot; Heilemann, Mike; Nir, Eyal; Weiss, Shimon

    2015-11-01

    Single-molecule fluorescence resonance energy transfer (smFRET) has been widely applied to the study of fluorescently labeled biomolecules on surfaces and in solution. Sorting single molecules based on fluorescent dye stoichiometry provides one with further layers of information and also enables "filtering" of unwanted molecules from the analysis. We accomplish this sorting by using alternating laser excitation (ALEX) in combination with smFRET measurements; here we describe the implementation of these methodologies for the study of biomolecules in solution. PMID:26527772

  1. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... Cerebral Palsy: Caring for Your Child All About Food Allergies How to Read a Nutrition Facts Label (Video) KidsHealth > For Parents > How to Read a Nutrition Facts Label (Video) Print A A A Text Size ... MORE ON THIS TOPIC Keeping Portions Under Control Figuring Out Food Labels Healthy Food Shopping If My Child Has ...

  2. 40 CFR 211.105 - Label format.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Label format. 211.105 Section 211.105 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS PRODUCT NOISE LABELING General Provisions § 211.105 Label format. (a) Unless specified otherwise in other...

  3. 21 CFR 701.11 - Identity labeling.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Identity labeling. 701.11 Section 701.11 Food and... COSMETIC LABELING Package Form § 701.11 Identity labeling. (a) The principal display panel of a cosmetic in package form shall bear as one of its principal features a statement of the identity of the commodity....

  4. What determines consumer attention to nutrition labels?

    NARCIS (Netherlands)

    Bialkova, S.E.; Trijp, van J.C.M.

    2010-01-01

    To identify the key determinants of consumer attention to nutrition labels, visual search tasks (present – absent; one – two targets) were used as an effective experimental tool. The main manipulation concerned: set size (number of labels on front of pack); label characteristics (display size, posit

  5. 21 CFR 225.80 - Labeling.

    Science.gov (United States)

    2010-04-01

    ... CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS Packaging and Labeling § 225.80 Labeling. (a... adhered to, will assure that the article is safe and effective for its intended purposes. (b)(1) Labels... medicated feed and includes adequate information for the safe and effective use of the medicated feed....

  6. 21 CFR 1271.250 - Labeling controls.

    Science.gov (United States)

    2010-04-01

    ...) General. You must establish and maintain procedures to control the labeling of HCT/Ps. You must design these procedures to ensure proper HCT/P identification and to prevent mix-ups. (b) Verification.... Procedures must ensure that each HCT/P is labeled in accordance with all applicable labeling...

  7. 201Tl labelled myocardium tomoscanning

    International Nuclear Information System (INIS)

    A new device, the J and P Tomoscanner, enables us to obtain the transverse scintigraphic section of any organ labelled by a single photon emitting radionuclide. For the time being, this technique has been used mainly for brain and liver studies. This work explores the ability of this tomograph to furnish sections of the 201Tl labelled myocardium by comparing them with the scintillation gamma-camera images. Towards this aim, witnesses and patients with documented anterior or lateral infarctus have been studied. Our actual results show a high correlation between the two explorations. But, by means of the section, both the site and size of the necrosis are visualized. However, only a single tomographic image was obtained in each patient because of the time necessary for its retranscription on paper. In the near future, when it will be possible to perform routinely several sections, a better size estimation will be possible

  8. Single Molecule Screening of Disease DNA Without Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Ji-Young Lee

    2006-12-12

    The potential of single molecule detection as an analysis tool in biological and medical fields is well recognized today. This fast evolving technique will provide fundamental sensitivity to pick up individual pathogen molecules, and therefore contribute to a more accurate diagnosis and a better chance for a complete cure. Many studies are being carried out to successfully apply this technique in real screening fields. In this dissertation, several attempts are shown that have been made to test and refine the application of the single molecule technique as a clinical screening method. A basic applicability was tested with a 100% target content sample, using electrophoretic mobility and multiple colors as identification tools. Both electrophoretic and spectral information of individual molecule were collected within a second, while the molecule travels along the flow in a capillary. Insertion of a transmission grating made the recording of the whole spectrum of a dye-stained molecule possible without adding complicated instrumental components. Collecting two kinds of information simultaneously and combining them allowed more thorough identification, up to 98.8% accuracy. Probing mRNA molecules with fluorescently labeled cDNA via hybridization was also carried out. The spectral differences among target, probe, and hybrid were interpreted in terms of dispersion distances after transmission grating, and used for the identification of each molecule. The probes were designed to have the least background when they are free, but have strong fluorescence after hybridization via fluorescence resonance energy transfer. The mRNA-cDNA hybrids were further imaged in whole blood, plasma, and saliva, to test how far a crude preparation can be tolerated. Imaging was possible with up to 50% of clear bio-matrix contents, suggesting a simple lysis and dilution would be sufficient for imaging for some cells. Real pathogen DNA of human papillomavirus (HPV) type-I6 in human genomic DNA

  9. Pharmaceuticals labelled with stable isotopes

    International Nuclear Information System (INIS)

    The relatively new field of pharmaceuticals labelled with stable isotopes is reviewed. Scientific, juridical, and ethical questions are discussed concerning the application of these pharmaceuticals in human medicine. 13C, 15N, and 2H are the stable isotopes mainly utilized in metabolic function tests. Methodical contributions are given to the application of 2H, 13C, and 15N pharmaceuticals showing new aspects and different states of development in the field under discussion. (author)

  10. Radioactively labelled vitamin B12

    International Nuclear Information System (INIS)

    A method is described for preparing radioactively labelled vitamin B 12 (cyanocobalamin) by reacting α-(5,6-dimethylbenzimidazolyl) hydrogenobamide with active (sup(57,58)Co) cobaltous ion. The latter may be in the form of cobaltous chloride or sulphate in aqueous or aqueous alcoholic medium. The reaction is effected by heating the reactants in darkness at pH 4 to 8. An excess of cyanide is added to convert the hydroxocobalamin formed to cyanocobalamin. (U.K.)

  11. The choice of label and measurement technique in tracer studies of body protein metabolism in man

    International Nuclear Information System (INIS)

    The turnover of non-serum proteins in man has had limited study despite the physiological importance of maintaining the balance between synthesis and breakdown of body proteins. Body protein is usually considered as a single pool and breakdown rates are often measured by monitoring excreted label at intervals after pulse labelling with radioactive or 15N amino acids. No label has yet been used for measuring tissue protein breakdown in man which is free from the major problem of label re-utilization. All measurements of breakdown rates, eg. with 75Se-selenomethionine, 15N- or 14C-glycine, give rate constants which are too low. The heterogeneity of body proteins also means that an estimate of the weighted average breakdown rate can only be obtained after following the excretion of isotope for a long period, perhaps of the order of 3-4 half-lives which, for man, would be 100 days after labelling. We therefore use infusions with either 14C- or 15N-labelled amino acids to measure breakdown and synthesis rates: these values are less affected by problems of protein heterogeneity. Single injection techniques are subject to more error than constant infusions of label because of the difficulty of defining the precursor activity. 15N labelling need not be confined to essential amino acids if total protein rather than amino acid turnover is studied: the latter involves measurements of the labelled amino acid itself which is difficult with 15N because of the small amounts of free amino acid nitrogen available. Carbon labelling of non-essential amino acids is unsuitable for studies of protein turnover and the choice of the position of the label on the molecule is important when labelled essential amino acids are employed. Short-term changes in protein metabolism are evaluated better with amino acids with a small pool size; the equilibration time in the excretory bicarbonate pool is also shorter than in the urea pool so that 15N is less useful than carbon labelling. We now use C

  12. Biomolecule labelling by 186 Re

    International Nuclear Information System (INIS)

    The aim of this study is to develop and improve the existing radiolabelling techniques of peptides and monoclonal antibodies with 186 Re and 188 Re as potential agents for cancer targeted radiotherapy. We selected the following methods and techniques for direct labelling of peptides and monoclonal antibody: 1. Prereduction of -S-S- bridges of biomolecule to sulfhydryls using reducing agents: ascorbic acid, cysteine, active hydrogen, 2,3 dimercaptopropanol. The prereduction reactions are controlled by massic ratios of reduction agents/biomolecule, pH, temperature and time of incubation; 2. Reduction of 186 Re O4- stannous chloride in acid and alkaline pH; 3. Coupling reaction of 186 Re (red) with the biomolecule controlled by the time and temperature of incubation, the influence of pH regarding the binding of 186 Re to the biomolecules. The quality control was effected by chromatography techniques (paper and elution gel chromatography) on labeled biomolecule before and after purification. The elution gel chromatography was spectrophotometricaly monitored at 280 nm. In the same time the radioactivity of samples was measured using a gamma counter. All the results confirm in vitro stability of labeled biomolecule. The biological evaluation studies regarding accumulation and biological affinity will be controlled by scintigraphy method. Biodistribution studies will be effected to Walker tumor bearing animals at 4 and 24 hours after injections. (authors)

  13. Glycation Reactivity of a Quorum-Sensing Signaling Molecule.

    Science.gov (United States)

    Tsuchikama, Kyoji; Gooyit, Major; Harris, Tyler L; Zhu, Jie; Globisch, Daniel; Kaufmann, Gunnar F; Janda, Kim D

    2016-03-14

    Reported herein is that (4S)-4,5-dihydroxy-2,3-pentanedione (DPD) can undergo a previously undocumented non-enzymatic glycation reaction. Incubation of DPD with viral DNA or the antibiotic gramicidin S resulted in significant biochemical alterations. A protein-labeling method was consequently developed that facilitated the identification of unrecognized glycation targets of DPD in a prokaryotic system. These results open new avenues toward tracking and understanding the fate and function of the elusive quorum-sensing signaling molecule. PMID:26890076

  14. Use of Symbols in Labeling. Final rule.

    Science.gov (United States)

    2016-06-15

    The Food and Drug Administration (FDA or the Agency) is issuing this final rule revising its medical device and certain biological product labeling regulations to explicitly allow for the optional inclusion of graphical representations of information, or symbols, in labeling (including labels) without adjacent explanatory text (referred to in this document as "stand-alone symbols") if certain requirements are met. The final rule also specifies that the use of symbols, accompanied by adjacent explanatory text continues to be permitted. FDA is also revising its prescription device labeling regulations to allow the use of the symbol statement "Rx only" or "[rx] only" in the labeling for prescription devices. PMID:27311137

  15. Eye tracking and nutrition label use

    DEFF Research Database (Denmark)

    Graham, Dan J.; Orquin, Jacob Lund; Visschers, Vivianne H.M.

    2012-01-01

    cameras monitoring consumer visual attention (i.e., eye tracking) has begun to identify ways in which label design could be modified to improve consumers’ ability to locate and effectively utilize nutrition information. The present paper reviews all published studies of nutrition label use that have......Nutrition labels on food packages are among the most prominent and far-reaching policy measures related to diet and have the capacity to promote healthy eating. Unfortunately, certain nutrition label characteristics may impede consumer detection and comprehension of labels. Research using precise...

  16. Improved quality control of carbon-14 labelled compounds

    International Nuclear Information System (INIS)

    IUT Ltd is a producer of carbon-14 labelled organic compounds like benzene, methanol, phenol, formaldehyde, Na-acetates and also special ordered compounds. The quality control of these compounds is carried out by means of HPLC and GC-MS due to chemical purity. Molar activity was determined by Liquid Scintillation Counting and HPLC being equipped by a radioactivity detector. Unfortunately the accuracy of the activity determination was arrived only ±4% relatively. This error is too high because of the large dilution factors. In respect of the IUT accreditation as an analytical laboratory in Germany the accuracy had to be improved remarkably. Therefore the GC-MS-determination of molar activities of labelled compounds is used as the 14C-labelled compound. A special evaluation code is used to determine the enrichment values relative to the unlabelled molecules. Taking into account the results of GC-MS the accuracy of molar activity determination is improved to ±2%. The spectra evaluation is demonstrated and some examples are discussed

  17. Correlative microscopy of densely labeled projection neurons using neural tracers

    Directory of Open Access Journals (Sweden)

    Daniele Oberti

    2010-06-01

    Full Text Available Three-dimensional morphological information about neural microcircuits is of high interest in neuroscience, but acquiring this information remains challenging. A promising new correlative technique for brain imaging is array tomography (Micheva and Smith, 2007, in which series of ultrathin brain sections are treated with fluorescent antibodies against neurotransmitters and synaptic proteins. Treated sections are repeatedly imaged in the fluorescence light microscope (FLM and then in the electron microscope (EM. We explore a similar correlative imaging technique in which we differentially label distinct populations of projection neurons, the key routers of electrical signals in the brain. In songbirds, projection neurons can easily be labeled using neural tracers, because the vocal control areas are segregated into separate nuclei. We inject tracers into areas afferent and efferent to the main premotor area for vocal production, HVC, to retrogradely and anterogradely label different classes of projection neurons. We optimize tissue preparation protocols to achieve high fluorescence contrast in the FLM and good ultrastructure in the EM (using osmium tetroxide. Although tracer fluorescence is lost during EM preparation, we localize the tracer molecules after fixation and embedding by using fluorescent antibodies against them. We detect signals mainly in somata and dendrites, allowing us to classify synapses within a single ultrathin section as belonging to a particular type of projection neuron. The use of our method will be to provide statistical information about connectivity among different neuron classes, and to elucidate how signals in the brain are processed and routed among different areas.

  18. Different Fluorophore Labeling Strategies and Designs Affect Millisecond Kinetics of DNA Hairpins

    Directory of Open Access Journals (Sweden)

    Andreas Hartmann

    2014-09-01

    Full Text Available Changes in molecular conformations are one of the major driving forces of complex biological processes. Many studies based on single-molecule techniques have shed light on conformational dynamics and contributed to a better understanding of living matter. In particular, single-molecule FRET experiments have revealed unprecedented information at various time scales varying from milliseconds to seconds. The choice and the attachment of fluorophores is a pivotal requirement for single-molecule FRET experiments. One particularly well-studied millisecond conformational change is the opening and closing of DNA hairpin structures. In this study, we addressed the influence of base- and terminal-labeled fluorophores as well as the fluorophore DNA interactions on the extracted kinetic information of the DNA hairpin. Gibbs free energies varied from ∆G0 = −3.6 kJ/mol to ∆G0 = −0.2 kJ/mol for the identical DNA hairpin modifying only the labeling scheme and design of the DNA sample. In general, the base-labeled DNA hairpin is significantly destabilized compared to the terminal-labeled DNA hairpin and fluorophore DNA interactions additionally stabilize the closed state of the DNA hairpin. Careful controls and variations of fluorophore attachment chemistry are essential for a mostly undisturbed measurement of the underlying energy landscape of biomolecules.

  19. Comparison of 90Y/177Lu labeled DOTA-Bz-RGD tetramer and DOTA-RGD tetramer

    International Nuclear Information System (INIS)

    90Y/177Lu labeled DOTA-Bz-RGD tetramer and DOTA-RGD tetramer were prepared, and the effect of Bz-DOTA and DOTA on labeling conditions and in vitro stability of radiolabeled compounds was compared. The labeling conditions, including reaction pH, reaction temperature and reaction time, were investigated. ITLC and HPLC show that the labeling yields of four radiolabeled compounds are more than 95% under optimal conditions (pH=6.0, reacting at 100 degree C for 15-20 min); the four radiolabeled compounds show pretty good stability in saline and fetal bovine serum. Although introducing of Bz has no effect on labeling conditions and in vitro stability of radiolabeled compounds, it brings a little change on molecule polarity. HPLC analysis and lg P values reveal that introducing of Bz increases the lipophilicity of radiolabeled compounds. (authors)

  20. Radionuclide labelling of a synthetic heparin-like polyelectrolyte and the adsorption of it onto silicone rubber

    International Nuclear Information System (INIS)

    This report describes attempts to prepare a radionuclide labelled polyelectrolyte tracer of adequate stability and specific activity to study the formation and stability of polyelectrolyte coatings for use as blood compatible materials in medical practice. Two kinds of polyelectrolyte were used, both prepared from polyisoprene, and three different labelling procedures were investigated. 125I and 35S were shown to be inadequate tracers but tritium was stably incorporated in the polyelectrolyte molecule with a labelling yield better than 90%. This tracer was then used to perform measurements pertaining to the binding and release of polyelectrolyte by a silicone rubber surface. Irradiation with gamma rays was shown to induce binding. (Auth./C.F.)

  1. The economics of GM food labels: An evaluation of mandatory labeling proposals in India

    OpenAIRE

    Bansal, Sangeeta; Ramaswami, Bharat

    2007-01-01

    "Labeling of genetically modified (GM) foods is a contentious issue and internationally, there is sharp division whether such labeling ought to be mandatory. This debate has reached India where the government has proposed mandatory labeling. In this context, this paper evaluates the optimal regulatory approach to GM food labels. Mandatory labeling aims to provide greater information and correspondingly more informed consumer choice. However, even without such laws, markets have incentives to ...

  2. Stable-isotope-labeled carbohydrates and nucleosides: Synthesis and applications in chemistry and biology

    Energy Technology Data Exchange (ETDEWEB)

    Serianni, A.S. [Univ. of Notre Dame, IN (United States)

    1994-12-01

    Carbohydrates play important roles in many key biochemical processes in living cells. For example, they are metabolized to produce energy, mediate cell-cell recognition, and play an indirect role (as constituents of DNA and RNA) in DNA replication, RNA transcription, and protein synthesis. These roles, and others of comparable biochemical significance, have been studied to varying extends with the use of stable isotopically labeled molecules, usually in conjunction with NMR spectroscopy and/or mass spectrometry. For example, carbohydrate metabolism has been monitored in vitro and in vivo with the use of isotopically labeled compounds. Molecular aspects of cell-cell recognition, mediated by cell-surface glycoproteins and glycolipids, have been probed through NMR studies of isotopically labeled oligosaccharides. More recently, the solution behavior of DNA and RNA has been examined through the use of labeled oligonucleotides. In all of these pursuits, the effort and expense to prepare labeled molecules, both of which can be substantial, are more than offset by the wealth of information derived from these studies. This information often cannot be accessed, or can be accessed only with great difficulty, using natural (unlabeled) compounds.

  3. Functionalized Polymer Microgel Particles Enable Customizable Production of Label-Free Sensor Arrays.

    Science.gov (United States)

    Lifson, Mark A; Carter, Jared A; Miller, Benjamin L

    2015-08-01

    Probe molecule immobilization onto surfaces is a critical step in the production of many analytical devices, including labeled and label-free microarrays. New methods to increase the density and uniformity of probe deposition have the potential to significantly enhance the ultimate limits of detection and reproducibility. Hydrogel-based materials have been employed in the past to provide a 3D protein-friendly surface for deposition of antibodies and nucleic acids. However, these methods are susceptible to variation during polymerization of the hydrogel scaffold and provide limited opportunities for tuning deposition parameters on an antibody-by-antibody basis. In this work, a versatile hydrogel nanoparticle deposition method was developed for the production of label-free microarrays and tested in the context of antibody-antigen binding. Poly(N-isopropylacrylamide) nanoparticles (PNIPAM) were conjugated to antibodies using an avidin/biotin system and deposited onto surfaces using a noncontact printing system. After drying, these gel spots formed uniform and thin layers <10 nm in height. The conjugates were characterized with dynamic light scattering, scanning electron microscopy, and atomic force microscopy. We tested this format in the context of tumor necrosis factor-alpha (TNF-α) detection via arrayed imaging reflectometry (AIR), a label-free protein microarray method. This method of probe molecule deposition should be generally useful in the production of microarrays for label-free detection. PMID:26140413

  4. Fluorescent labeling and tracking of nanoclay

    Science.gov (United States)

    Diaz, Carlos A.; Xia, Yining; Rubino, Maria; Auras, Rafael; Jayaraman, Krishnamurthy; Hotchkiss, Joseph

    2012-12-01

    We report a methodology developed to detect and track stable fluorescent-labeled nanoclay, in polymer-clay nanocomposite films, and in a contact solvent after migration testing. Fluorescein-5-maleimide (fluorescein) or tetramethylrhodamine-5-maleimide (rhodamine) was covalently bonded to organically modified montmorillonite (o-MMT). Fluorescein- and rhodamine-labeled nanoclay showed good thermal stability up to 220 °C and the rhodamine-labeled nanoclay remained stable at 250 °C. Confocal laser scanning microscopy was used to confirm the tagging and to detect the fluorescent-labeled nanoclays in various systems.We report a methodology developed to detect and track stable fluorescent-labeled nanoclay, in polymer-clay nanocomposite films, and in a contact solvent after migration testing. Fluorescein-5-maleimide (fluorescein) or tetramethylrhodamine-5-maleimide (rhodamine) was covalently bonded to organically modified montmorillonite (o-MMT). Fluorescein- and rhodamine-labeled nanoclay showed good thermal stability up to 220 °C and the rhodamine-labeled nanoclay remained stable at 250 °C. Confocal laser scanning microscopy was used to confirm the tagging and to detect the fluorescent-labeled nanoclays in various systems. Electronic supplementary information (ESI) available: Additional information regarding production of nanocomposites, the silylation procedure, labeling of the nanoclays, characterization of the labels, thermal stability of the labels, and the migration test. See DOI: 10.1039/c2nr32978f

  5. 75 FR 29775 - Food Labeling Workshop; Public Workshop

    Science.gov (United States)

    2010-05-27

    ... be discussed at the workshop include: (1) Mandatory label elements, (2) nutrition labeling... labeling and nutrition. FDA expects that participation in this public workshop will provide regulated... with labeling requirements, especially in light of growing concerns about obesity and food...

  6. Dengue virus growth, purification, and fluorescent labeling.

    Science.gov (United States)

    Zhang, Summer; Chan, Kuan Rong; Tan, Hwee Cheng; Ooi, Eng Eong

    2014-01-01

    The early events of the dengue virus life cycle involve virus binding, internalization, trafficking, and fusion. Fluorescently labeled viruses can be used to visualize these early processes. As dengue virus has 180 identical copies of the envelope protein attached to the membrane surface and is surrounded by a lipid membrane, amine-reactive (Alexa Fluor) or lipophilic (DiD) dyes can be used for virus labeling. These dyes are highly photostable and are ideal for studies involving cellular uptake and endosomal transport. To improve virus labeling efficiency and minimize the nonspecific labeling of nonviral proteins, virus concentration and purification precede fluorescent labeling of dengue viruses. Besides using these viruses for single-particle tracking, DiD-labeled viruses can also be used to distinguish serotype-specific from cross-neutralizing antibodies. Here the details of virus concentration, purification, virus labeling, applications, and hints of troubleshooting are described. PMID:24696327

  7. When water molecules meet air

    OpenAIRE

    Hsie, Cho-Shuen; Campen, R. Kramer; Verde, Ana Vila; Bolhuis, Peter; Nienhuys, Han-Kwang; Bonn, Mischa

    2012-01-01

    About 70% of our planet is covered in water. Most of that water exists as water in the bulk – the neighbors of water molecules are other water molecules – and only a small fraction of molecules are at the air-water interface. Despite the small relative abundance of interfacial water, it is of the utmost importance: it governs the chemistry involving the surface of oceans and seawater aerosols, or the small water droplets forming clouds. Reactions at the air-water interface are directly releva...

  8. Quantum transport through aromatic molecules

    International Nuclear Information System (INIS)

    In this paper, we study the electronic transport properties through aromatic molecules connected to two semi-infinite leads. The molecules are in different geometrical configurations including arrays. Using a nearest neighbor tight-binding approach, the transport properties are analyzed into a Green's function technique within a real-space renormalization scheme. We calculate the transmission probability and the Current-Voltage characteristics as a function of a molecule-leads coupling parameter. Our results show different transport regimes for these systems, exhibiting metal-semiconductor-insulator transitions and the possibility to employ them in molecular devices

  9. On randomized online labeling with polynomially many labels

    Czech Academy of Sciences Publication Activity Database

    Bulánek, Jan; Koucký, Michal; Saks, M.

    Berlin: Springer, 2013 - (Fomin, F.; Freivalds, R.; Kwiatkowska, M.; Peleg, D.), s. 291-302. (Lecture Notes in Computer Science. 7965). ISBN 978-3-642-39205-4. [International Colloquium, ICALP 2013 /40./. Riga (LT), 08.07.2013-12.07.2013] R&D Projects: GA AV ČR IAA100190902; GA ČR GBP202/12/G061 Institutional support: RVO:67985840 Keywords : online labeling * complexity Subject RIV: BA - General Mathematics http://link.springer.com/chapter/10.1007%2F978-3-642-39206-1_25

  10. Blocking of s-triazine molecules by organic matter

    International Nuclear Information System (INIS)

    Study of the variation in the rate of extraction of atrazine by methanol or water in experiments on the incubation of soil treated with this herbicide is a means of determining the active role of organic matter in the disappearance of phytotoxicity; 30-40% of the 14C-labelled product is very rapidly removed from the amount applied and therefore possibly from its herbicidal function. In the 'detoxification' process the fulvic acids and the humins play a predominant part. However, whereas the humic acids form stable bonds with s-triazine molecules, the fulvic acids and humins indicate the existence of low-energy bonds, suggesting that certain molecules fixed by the organic matter may contribute, by a process of release, to new states of equilibrium in the soil solution. (author)

  11. Enhanced Vibrational Spectroscopies as Tools for Small Molecule Biosensing

    Directory of Open Access Journals (Sweden)

    Souhir Boujday

    2015-08-01

    Full Text Available In this short summary we summarize some of the latest developments in vibrational spectroscopic tools applied for the sensing of (small molecules and biomolecules in a label-free mode of operation. We first introduce various concepts for the enhancement of InfraRed spectroscopic techniques, including the principles of Attenuated Total Reflection InfraRed (ATR-IR, (phase-modulated InfraRed Reflection Absorption Spectroscopy (IRRAS/PM-IRRAS, and Surface Enhanced Infrared Reflection Absorption Spectroscopy (SEIRAS. Particular attention is put on the use of novel nanostructured substrates that allow for the excitation of propagating and localized surface plasmon modes aimed at operating additional enhancement mechanisms. This is then be complemented by the description of the latest development in Surface- and Tip-Enhanced Raman Spectroscopies, again with an emphasis on the detection of small molecules or bioanalytes.

  12. A nucleotide-independent cyclic nitroxide label for monitoring segmental motions in nucleic acids

    International Nuclear Information System (INIS)

    Spin labels, which are chemically stable radicals attached at specific sites of a bio-molecule, enable investigations on structure and dynamics of proteins and nucleic acids using techniques such as site-directed spin labeling and paramagnetic NMR. Among spin labels developed, the class of rigid labels have limited or no independent motions between the radical bearing moiety and the target, and afford a number of advantages in measuring distances and monitoring local dynamics within the parent bio-molecule. However, a general method for attaching a rigid label to nucleic acids in a nucleotide-independent manner has not been reported. We developed an approach for installing a nearly rigid nitroxide spin label, designated as R5c, at a specific site of the nucleic acid backbone in a nucleotide-independent manner. The method uses a post-synthesis approach to covalently attach the nitroxide moiety in a cyclic fashion to phosphorothioate groups introduced at two consecutive nucleotides of the target strand. R5c-labeled nucleic acids are capable of pairing with their respective complementary strands, and the cyclic nature of R5c attachment significantly reduced independence motions of the label with respect to the parent duplex, although it may cause distortion of the local environment at the site of labeling. R5c yields enhanced sensitivity to the collective motions of the duplex, as demonstrated by its capability to reveal changes in collective motions of the substrate recognition duplex of the 120-kDa Tetrahymena group I ribozyme, which elude detection by a flexible label. The cyclic R5c nitroxide can be efficiently attached to a target nucleic acid site using a post-synthetic coupling approach conducted under mild biochemical conditions, and serves as a viable label for experimental investigation of segmental motions in nucleic acids, including large folded RNAs. The online version of this article (doi:10.1186/s13628-015-0019-5) contains supplementary material, which

  13. Radioactively labelled vitamin B12

    International Nuclear Information System (INIS)

    The application concerns the manufacture of radioactive forms of vitamin B-12 in which the cobalt atom present in the vitamin B-12 molecule is replaced with a radioactive isotope of cobalt, usually cobalt-57 or cobalt-58. Such radioactive forms of B-12 are used extensively in the diagnosis of B-12 deficiency states

  14. Theoretical Investigations Regarding Single Molecules

    DEFF Research Database (Denmark)

    Pedersen, Kim Georg Lind

    interfere destructively or constructively. Destructive interference effects in electron transport could potentially improve thermo-electrics, organic logic circuits and energy harvesting. We have investigated destructive interference in off-resonant transport through organic molecules, and have found a set...

  15. Polar molecule dominated electrorheological effect

    Institute of Scientific and Technical Information of China (English)

    Lu Kun-Quan; Shen Rong; Wang Xue-Zhao; Sun Gang; Wen Wei-Jia; Liu Ji-Xing

    2006-01-01

    The yield stress of our newly developed electrorheological (ER) fluids consisting of dielectric nano-particles suspended in silicone oil reaches hundreds of kPa, which is orders of magnitude higher than that of conventional ones. We found that the polar molecules adsorbed on the particles play a decisive role in such new ER fluids. To explain this polar molecule dominated ER (PM-ER) effect a model is proposed based on the interaction of polar molecule-charge between the particles, where the local electric field is significantly enhanced and results in the polar molecules aligning in the direction of the electric field. The model can well explain the giant ER effect and a near-linear dependence of the yield stress on the electric field. The main effective factors for achieving high-performance PM-ER fluids are discussed. The PM-ER fluids with the yield stress higher than one MPa can be expected.

  16. Nuclear molecules with three clusters

    International Nuclear Information System (INIS)

    Full text: Recently, in the cold fusion of 252 Cf, indications where found for the existence of nuclear molecules with three clusters. The system identified is 96 Sr + 10 Be + 146 Ba. In the first half of the talk the geometric model for three-cluster molecules is resumed and calculations done are presented. Problems and restrictions of the geometric model will be discussed. In the second half an Ansatz for an algebraic model for nuclear molecules is given. In a first step we restrict to two clusters only, which might have an application to standard two-cluster molecules. A Hamiltonian is proposed. The mapping to a geometric potential is described, which is fitted to the calculation of internuclear potentials using double-folding techniques. (Author)

  17. Single-Molecule DNA Analysis

    Science.gov (United States)

    Efcavitch, J. William; Thompson, John F.

    2010-07-01

    The ability to detect single molecules of DNA or RNA has led to an extremely rich area of exploration of the single most important biomolecule in nature. In cases in which the nucleic acid molecules are tethered to a solid support, confined to a channel, or simply allowed to diffuse into a detection volume, novel techniques have been developed to manipulate the DNA and to examine properties such as structural dynamics and protein-DNA interactions. Beyond the analysis of the properties of nucleic acids themselves, single-molecule detection has enabled dramatic improvements in the throughput of DNA sequencing and holds promise for continuing progress. Both optical and nonoptical detection methods that use surfaces, nanopores, and zero-mode waveguides have been attempted, and one optically based instrument is already commercially available. The breadth of literature related to single-molecule DNA analysis is vast; this review focuses on a survey of efforts in molecular dynamics and nucleic acid sequencing.

  18. Absorption characteristics of bacteriorhodopsin molecules

    Indian Academy of Sciences (India)

    H K T Kumar; K Appaji Gowda

    2000-03-01

    The bacteriorhodopsin molecule absorbs light and undergoes a series of structural transformation following a well-defined photocycle. The complex photocycle is transformed to an equivalent level diagram by considering the lifetime of the intermediate states. Assuming that only and states are appreciably populated at any instant of time, the level diagram is further simplified to two-level system. Based on the rate equations for two-level system, an analytic expression for the absorption coefficient of bacteriorhodopsin molecule is derived. It is applied to study the behaviour of absorption coefficient of bacteriorhodopsin film in the visible wavelength region of 514 nm. The dependence of absorption coefficient of bacteriorhodopsin film on the thickness of the film, total number density of active molecules and initial number density of molecules in -state is presented in the graphical form.

  19. Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor

    Science.gov (United States)

    Ferrie, Ann M.; Sun, Haiyan; Fang, Ye

    2011-07-01

    We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.

  20. Ultracold molecules and ultracold chemistry

    OpenAIRE

    Softley, Tim; Bell, Martin

    2009-01-01

    Abstract The recent development of a range of new methods for producing samples of gas phase molecules that are translationally cold (T < 1 K) or ultracold (T < 1 mK) is driving efforts to study reactive and inelastic collisional processes in these temperature regimes. In this review article the new methods for cold/ultracold molecule production are reviewed in the context of their potential or current use in collisional studies and progress in the application of these methods i...

  1. Hemoglobin Labeled by Radioactive Lysine

    Science.gov (United States)

    Bale, W. F.; Yuile, C. L.; DeLaVergne, L.; Miller, L. L.; Whipple, G. H.

    1949-12-08

    This paper reports on the utilization of tagged epsilon carbon of DL-lysine by a dog both anemic and hypoproteinemic due to repeated bleeding plus a diet low in protein. The experiment extended over period of 234 days, a time sufficient to indicate an erythrocyte life span of at least 115 days based upon the rate of replacement of labeled red cell proteins. The proteins of broken down red cells seem not to be used with any great preference for the synthesis of new hemoglobin.

  2. Classical complement pathway activation by antipneumococcal antibodies leads to covalent binding of C3b to antibody molecules.

    OpenAIRE

    Brown, E J; Berger, M.; Joiner, K A; Frank, M. M.

    1983-01-01

    We have examined whether or not a physical relationship exists between antipneumococcal antibodies (Ab) and C3b when Ab activate the classical complement pathway on the surface of pneumococci (Pn). After sensitization with 125I-labeled Ab, Pn were sequentially incubated with purified C1, C4, C2, and biotinylated C3. Ab molecules were then eluted from Pn, and C3b-associated molecules were purified on avidin-Sepharose. Both 125I-labeled immunoglobulin G (IgG) and [125I]IgM bound to C3b; the ass...

  3. Probing a label-free local bend in DNA by single-molecule Tethered Particle Motion

    OpenAIRE

    Brunet, Annaël; Chevalier, Sébastien; Destainville, Nicolas; Manghi, Manoel; Rousseau, Philippe; Salhi, Maya; Salomé, Laurence; Tardin, Catherine

    2015-01-01

    Being capable of characterizing DNA local bending is essential to understand thoroughly many biological processes because they involve a local bending of the double helix axis, either intrinsic to the sequence or induced by the binding of proteins. Developing a method to measure DNA bend angles that does not perturb the conformation of the DNA itself or the DNA-protein complex is a challenging task. Here, we propose a joint theory-experiment high throughput approach to rigorously measure such...

  4. Probing a label-free local bend in DNA by single molecule tethered particle motion

    OpenAIRE

    Brunet, Annaël; Chevalier, Sébastien; Destainville, Nicolas; Manghi, Manoel; Rousseau, Philippe; Salhi, Maya; Salomé, Laurence; Tardin, Catherine

    2015-01-01

    Being capable of characterizing DNA local bending is essential to understand thoroughly many biological processes because they involve a local bending of the double helix axis, either intrinsic to the sequence or induced by the binding of proteins. Developing a method to measure DNA bend angles that does not perturb the conformation of the DNA itself or the DNA-protein complex is a challenging task. Here, we propose a joint theory-experiment high-throughput approach to rigorously measure such...

  5. PLLA-PEG-TCH-labeled bioactive molecule nanofibers for tissue engineering

    OpenAIRE

    Chen J; Zhou B; Li Q; Ouyang J; Kong J; Zhong W; Xing MM

    2011-01-01

    Jun Chen1,2, Beth Zhou1–3, Qi Li1,2, Jun Ouyang4, Jiming Kong2,4,5, Wen Zhong3,6, Malcolm MQ Xing1,2,4,71Department of Mechanical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada; 2Manitoba Institute of Child Health, Winnipeg, MB, Canada; 3Department of Textile Sciences, Faculty of Human Ecology, University of Manitoba, Winnipeg, MB, Canada; 4School of Basic Medical Science, Southern Medical University, Guangzhoug, China; 5Department of Human Anatomy...

  6. Photoaffinity labeling demonstrates binding between Ia molecules and nominal antigen on antigen-presenting cells.

    OpenAIRE

    Phillips, M L; Yip, C C; Shevach, E M; Delovitch, T L

    1986-01-01

    We have used radioiodinated photoreactive bovine insulin as antigen to examine the molecular nature of immunogenic complexes that form on antigen-presenting cells. The probe was allowed to bind to either insulin-presenting B-hybridoma cells, lipopolysaccharide-stimulated blasts, or bovine insulin-specific helper-T-hybridoma cells in the dark. Samples were then exposed to light to induce crosslinkage, solubilized, and analyzed by gel electrophoresis. Two protein bands at about 36 kDa and 27 kD...

  7. Confocal microscopy on fluorescently labelled single DNA molecules and force-extension measurements on DNA carpets

    OpenAIRE

    Lehner, Roman

    2005-01-01

    Ziel dieser Arbeit ist es chemische, molekularbiologische und physikalische Methoden zu entwickeln die es erlauben ein Ensemble von DNA Molekülen in definierter Weise zu strecken. Dies soll strukturanalytische Untersuchungen des B-S Übergangs von DNA erlauben, was zur Aufklärung der Wechselwirkung von DNA mit dem RecA protein beitragen könnte. RecA ist ein Protein, das für die Rekombination in E.coli verantwortlich ist. Um Kraft-Dehnungskurven an einem Ensemble von DNA Molekülen zu messen wur...

  8. Protein labelling with avidin-biotin systems

    International Nuclear Information System (INIS)

    The stability of connection in avidin-biotin system is very important due to the quadruple connections with avidin established with the same number of biotin molecules, which can amplify damage on cancer cells and increase specific activity of radio immuno conjugate in white cell. If between the first and second step (Ac Mo-biotin + avidin) enough time is left so that the monoclonal antibody accumulates in a therapeutic concentration required for the tumor or cancerous cells, then upon application of the third step (biotin-DTPA-153 Sm) it is hoped that in the first 30 minutes after application, only radioactivity remains with tumor. However, so that the amount radioactivity is enough to destroy a tumor, it would be necessary to use 153 Sm with an activity of approximately 370 GBq (10 Ci)/ (mg). Since 99m Tc has similar chemistry to that of the 188 Re, it is possible to propose their conjugates with biotin-avidin-Ac Mo-188 Re as a powerful option for therapeutic applications, this is, recommending the use of biotinylated labelled monoclonal antibody and the further injection of avidin to decrease of desirable effects on several other organs and bone marrow and high specific and selective action on tumor. On the other hand, we postulate the hypothesis in the sense that 188 Re complexes tend to be more stable than those of 99m Tc, probably due to their metabolism, in which radioactivity of 188 Re, not captured by tumor, is cleared easily from blood stream which results in a decrease of total and liver total dose in patient. (Author)

  9. Label transfer by measuring compactness.

    Science.gov (United States)

    Varga, Robert; Nedevschi, Sergiu

    2013-12-01

    This paper presents a new automatic image annotation algorithm. First, we introduce a new similarity measure between images: compactness. This uses low level visual descriptors for determining the similarity between two images. Compactness shows how close test image features lie to training image feature cluster centers. The measure provides the core for a k-nearest neighbor type image annotation method. Afterward, a formalism for defining different transfer techniques is devised and several label transfer techniques are provided. The method as whole is evaluated on four image annotation benchmarks. The results on these sets validate the accuracy of the approach, which outperforms many state-of-the-art annotation methods. The method presented here requires a simple training process, efficiently combines different feature types and performs better than complex learning algorithms, even in this incipient form. The main contributions of this paper are the usage of compactness as a similarity measure that enables efficient low level feature comparison and an annotation algorithm based on label transfer. PMID:23955754

  10. Label Space Reduction in MPLS Networks: How Much Can A Single Stacked Label Do?

    DEFF Research Database (Denmark)

    Solano, Fernando; Stidsen, Thomas K.; Fabregat, Ramon;

    2008-01-01

    Most network operators have considered reducing LSR label spaces (number of labels used) as a way of simplifying management of underlaying virtual private networks (VPNs) and therefore reducing operational expenditure (OPEX). The IETF outlined the label merging feature in MPLS-allowing the config......Most network operators have considered reducing LSR label spaces (number of labels used) as a way of simplifying management of underlaying virtual private networks (VPNs) and therefore reducing operational expenditure (OPEX). The IETF outlined the label merging feature in MPLS...

  11. Link Label Prediction in Signed Citation Network

    KAUST Repository

    Akujuobi, Uchenna

    2016-04-12

    Link label prediction is the problem of predicting the missing labels or signs of all the unlabeled edges in a network. For signed networks, these labels can either be positive or negative. In recent years, different algorithms have been proposed such as using regression, trust propagation and matrix factorization. These approaches have tried to solve the problem of link label prediction by using ideas from social theories, where most of them predict a single missing label given that labels of other edges are known. However, in most real-world social graphs, the number of labeled edges is usually less than that of unlabeled edges. Therefore, predicting a single edge label at a time would require multiple runs and is more computationally demanding. In this thesis, we look at link label prediction problem on a signed citation network with missing edge labels. Our citation network consists of papers from three major machine learning and data mining conferences together with their references, and edges showing the relationship between them. An edge in our network is labeled either positive (dataset relevant) if the reference is based on the dataset used in the paper or negative otherwise. We present three approaches to predict the missing labels. The first approach converts the label prediction problem into a standard classification problem. We then, generate a set of features for each edge and then adopt Support Vector Machines in solving the classification problem. For the second approach, we formalize the graph such that the edges are represented as nodes with links showing similarities between them. We then adopt a label propagation method to propagate the labels on known nodes to those with unknown labels. In the third approach, we adopt a PageRank approach where we rank the nodes according to the number of incoming positive and negative edges, after which we set a threshold. Based on the ranks, we can infer an edge would be positive if it goes a node above the

  12. Effect of polysaccharide capsule of the microalgae Staurastrum iversenii var. americanum on diffusion of charged and uncharged molecules, using EPR technique

    International Nuclear Information System (INIS)

    The existence of a mucilaginous envelope, sheath or capsule is usual in many desmids, but few data concerning its function are available. Previous studies of the transport function and permeation of molecules through the algae capsules were done using the algae Spondylosium panduriforme and Nephrocytium lunatum, the Electron Paramagnetic Resonance (EPR) technique, and different spin labels. The results suggested that the capsule functions as a selective diffusion medium. In the present work charged and uncharged molecules (spin labels group A) and Staurastrum iversenii var. americanum (Desmids),whose alga presents a great mucilaginous capsule, were used. Charged nitroxide molecules similar to amino acids (spin labels group B) were also used allowing a better understanding of the electrostatic effect in the permeation process across the capsule. The role of the cell capsule in the solute diffusion was evaluated by determining the capsulated and decapsulated cell permeation times. The permeation times for all spin labels tested in the cells lacking capsules were always shorter than those containing this physical barrier. The decay times of spin labels group A observed for S. iversenii were compared to other studied algae. The results regarding the diffusion of charged spin labels group B suggested that the interaction of cell capsule occurs more strongly with negatively charged molecules than with positively charged ones. The results obtained in this work with spin labels group A confirm that the capsule is an essential structure for the cell, and that due to the polar interactions with the spin labels, it plays an important role in the selection of small molecules. Several parameters, mainly those of electrostatic nature, seem to control the permeation across the algal capsules of spin labels group B, showing that structures which are similar to amino acids could diffuse across the interior of the algal cell. (author)

  13. GOLD CLUSTER LABELS AND RELATED TECHNOLOGIES IN MOLECULAR MORPHOLOGY.

    Energy Technology Data Exchange (ETDEWEB)

    HAINFELD,J.F.; POWELL,R.D.

    2004-02-04

    Although intensely colored, even the largest colloidal gold particles are not, on their own, sufficiently colored for routine use as a light microscopy stain: only with very abundant antigens or with specialized illumination methods can bound gold be seen. Colloidal gold probes were developed primarily as markers for electron microscopy, for which their very high electron density and selectivity for narrow size distributions when prepared in different ways rendered them highly suited. The widespread use of gold labeling for light microscopy was made possible by the introduction of autometallographic enhancement methods. In these processes, the bound gold particles are exposed to a solution containing metal ions and a reducing agent; they catalyze the reduction of the ions, resulting in the deposition of additional metal selectively onto the particles. On the molecular level, the gold particles are enlarged up to 30-100 nm in diameter; on the macroscale level, this results in the formation of a dark stain in regions containing bound gold particles, greatly increasing visibility and contrast. The applications of colloidal gold have been described elsewhere in this chapter, we will focus on the use of covalently linked cluster complexes of gold and other metals. A gold cluster complex is a discrete molecular coordination compound comprising a central core, or ''cluster'' of electron-dense metal atoms, ligated by a shell of small organic molecules (ligands), which are linked to the metal atoms on the surface of the core. This structure gives clusters several important advantages as labels. The capping of the metal surface by ligands prevents non-specific binding to cell and tissue components, which can occur with colloidal gold. Cluster compounds are more stable and may be used under a wider range of conditions. Unlike colloidal gold, clusters do not require additional macromolecules such as bovine serum albumin or polyethylene glycol for

  14. Raman Optical Activity Spectra for Large Molecules through Molecules-in-Molecules Fragment-Based Approach.

    Science.gov (United States)

    Jovan Jose, K V; Raghavachari, Krishnan

    2016-02-01

    We present an efficient method for the calculation of the Raman optical activity (ROA) spectra for large molecules through the molecules-in-molecules (MIM) fragment-based method. The relevant higher energy derivatives from smaller fragments are used to build the property tensors of the parent molecule to enable the extension of the MIM method for evaluating ROA spectra (MIM-ROA). Two factors were found to be particularly important in yielding accurate results. First, the link-atom tensor components are projected back onto the corresponding host and supporting atoms through the Jacobian projection method, yielding a mathematically rigorous method. Second, the long-range interactions between fragments are taken into account by using a less computationally expensive lower level of theory. The performance of the MIM-ROA model is calibrated on the enantiomeric pairs of 10 carbohydrate benchmark molecules, with strong intramolecular interactions. The vibrational frequencies and ROA intensities are accurately reproduced relative to the full, unfragmented, results for these systems. In addition, the MIM-ROA method is employed to predict the ROA spectra of d-maltose, α-D-cyclodextrin, and cryptophane-A, yielding spectra in excellent agreement with experiment. The accuracy and performance of the benchmark systems validate the MIM-ROA model for exploring ROA spectra of large molecules. PMID:26760444

  15. Vibrational Circular Dichroism Spectra for Large Molecules through Molecules-in-Molecules Fragment-Based Approach.

    Science.gov (United States)

    Jose, K V Jovan; Beckett, Daniel; Raghavachari, Krishnan

    2015-09-01

    We present the first implementation of the vibrational circular dichroism (VCD) spectrum of large molecules through the Molecules-in-Molecules (MIM) fragment-based method. An efficient projection of the relevant higher energy derivatives from smaller fragments to the parent molecule enables the extension of the MIM method for the evaluation of VCD spectra (MIM-VCD). The overlapping primary subsystems in this work are constructed from interacting fragments using a number-based scheme and the dangling bonds are saturated with link hydrogen atoms. Independent fragment calculations are performed to evaluate the energies, Hessian matrix, atomic polar tensor (APT), and the atomic axial tensor (AAT). Subsequently, the link atom tensor components are projected back onto the corresponding host and supporting atoms through the Jacobian projection method, as in the ONIOM approach. In the two-layer model, the long-range interactions between fragments are accounted for using a less computationally intensive lower level of theory. The performance of the MIM model is calibrated on the d- and l-enantiomers of 10 carbohydrate benchmark molecules, with strong intramolecular interactions. The vibrational frequencies and VCD intensities are accurately reproduced relative to the full, unfragmented, results for these systems. In addition, the MIM-VCD method is employed to predict the VCD spectra of perhydrotriphenylene and cryptophane-A, yielding spectra in agreement with experiment. The accuracy and performance of the benchmark systems validate the MIM-VCD model for exploring vibrational circular dichroism spectra of large molecules. PMID:26575919

  16. The Molecule Cloud - compact visualization of large collections of molecules

    Directory of Open Access Journals (Sweden)

    Ertl Peter

    2012-07-01

    Full Text Available Abstract Background Analysis and visualization of large collections of molecules is one of the most frequent challenges cheminformatics experts in pharmaceutical industry are facing. Various sophisticated methods are available to perform this task, including clustering, dimensionality reduction or scaffold frequency analysis. In any case, however, viewing and analyzing large tables with molecular structures is necessary. We present a new visualization technique, providing basic information about the composition of molecular data sets at a single glance. Summary A method is presented here allowing visual representation of the most common structural features of chemical databases in a form of a cloud diagram. The frequency of molecules containing particular substructure is indicated by the size of respective structural image. The method is useful to quickly perceive the most prominent structural features present in the data set. This approach was inspired by popular word cloud diagrams that are used to visualize textual information in a compact form. Therefore we call this approach “Molecule Cloud”. The method also supports visualization of additional information, for example biological activity of molecules containing this scaffold or the protein target class typical for particular scaffolds, by color coding. Detailed description of the algorithm is provided, allowing easy implementation of the method by any cheminformatics toolkit. The layout algorithm is available as open source Java code. Conclusions Visualization of large molecular data sets using the Molecule Cloud approach allows scientists to get information about the composition of molecular databases and their most frequent structural features easily. The method may be used in the areas where analysis of large molecular collections is needed, for example processing of high throughput screening results, virtual screening or compound purchasing. Several example visualizations of large

  17. Radiopharmaceutical potential of I-131 labelled diazepam

    International Nuclear Information System (INIS)

    In this study, diazepam is a derivative of the 1.4 benzodiazepine family that the most widely used drug as anticonvulsant agent has been labeled with I-131, as a new radiopharmaceutical and its radiopharmaceutical potential has been determined. Labeling of diazepam has been performed by iodogen method and optimum labeling conditions have been determined. Optimum reaction conditions are 1 mg for iodogen amount; 1-5 mg for diazepam amount, 15-20 minutes for reaction time and room temperature for reaction temperature. Specific activity of labeled compound was 0,15 Ci/mmol level. N-octanol/water ratio was found 1.9 for 131IDZ (131I labeled diazepam). In vivo experiments have been carried out to determine radiopharmaceutical potentials of labeled compound. Biodistribution studies on rats showed that 131IDZ have accumulated in kidneys, liver, lungs and brain tissues. Scintigraphic results taken with gamma camera on rabbits agree with biodistribution results of rats. (author)

  18. Irradiation test of bar code label

    International Nuclear Information System (INIS)

    The irradiation test of bar code label tagged on radioactive waste container was done to determine the effect of radiation. Low and medium radioactive waste is that below total activity of 4,000Bq/g according to the Korean nuclear law. The irradiation amount to radiate bar code label tagged on radioactive waste container was calculated by MCNP-4b computer code. The nuclide such as Co-60 and Cs-137 was assumed to contribute 50 % of total activity. Real irradiation amount for bar code label was finally calculated by the dimensions of the container and the bar code label. The identification of post and the physical deflection of irradiated bar code label was tested by the bar code reader. The coated bar code label was suitable to use on low and medium radioactive waste container

  19. Green power: naturemade - History of a label

    International Nuclear Information System (INIS)

    This article presents the history of the set of 'naturemade' labels that are used to designate power generated in facilities that use renewable energy. Electricity from hydropower, wind-power, biogas and solar energy plants that fulfil particular ecological conditions receives a special label, 'Naturemade Star'. 'Normal' hydropower can be awarded the 'Naturemade Basic' label. The development of the labels is discussed in the light of increasing liberalisation of European electricity markets and increasing sales of 'green power' by electricity utilities. The need for certification of production facilities and the founding of the label's certification authority, the 'Verein fuer umweltgerechte Elektrizitaet' (VUE), a society for the promotion of environment-friendly electricity, are discussed. Criticisms made by certain environmental protection organisations on the awarding of the 'Naturemade Basic' label to projects that in their opinion do not help protect the environment are quoted. The article is completed with an interview on the subject with Ursula Stocker from the VUE

  20. Single Molecule Fluorescence Measurements of Ribosomal Translocation Dynamics

    Science.gov (United States)

    Chen, Chunlai; Stevens, Benjamin; Kaur, Jaskarin; Cabral, Diana; Liu, Hanqing; Wang, Yuhong; Zhang, Haibo; Rosenblum, Gabriel; Smilansky, Zeev; Goldman, Yale E.; Cooperman, Barry S.

    2011-01-01

    We employ single-molecule fluorescence resonance energy transfer (smFRET) to study structural dynamics over the first two elongation cycles of protein synthesis, using ribosomes containing either Cy3-labeled ribosomal protein L11 and A- or P-site Cy5-labeled tRNA or Cy3 and Cy5 labeled tRNAs. Pre-translocation (PRE) complexes demonstrate fluctuations between classical and hybrid forms, with concerted motions of tRNAs away from L11 and from each other when classical complex converts to hybrid complex. EF-G·GTP binding to both hybrid and classical PRE complexes halts these fluctuations prior to catalyzing translocation to form the post-translocation (POST) complex. EF-G dependent translocation from the classical PRE complex proceeds via transient formation of a short-lived hybrid intermediate. A-site binding of either EF-G to the PRE complex or of aminoacyl-tRNA·EF-Tu ternary complex to the POST complex markedly suppresses ribosome conformational lability. PMID:21549313

  1. Single-molecule fluorescence measurements of ribosomal translocation dynamics.

    Science.gov (United States)

    Chen, Chunlai; Stevens, Benjamin; Kaur, Jaskarin; Cabral, Diana; Liu, Hanqing; Wang, Yuhong; Zhang, Haibo; Rosenblum, Gabriel; Smilansky, Zeev; Goldman, Yale E; Cooperman, Barry S

    2011-05-01

    We employ single-molecule fluorescence resonance energy transfer (smFRET) to study structural dynamics over the first two elongation cycles of protein synthesis, using ribosomes containing either Cy3-labeled ribosomal protein L11 and A- or P-site Cy5-labeled tRNA or Cy3- and Cy5-labeled tRNAs. Pretranslocation (PRE) complexes demonstrate fluctuations between classical and hybrid forms, with concerted motions of tRNAs away from L11 and from each other when classical complex converts to hybrid complex. EF-G⋅GTP binding to both hybrid and classical PRE complexes halts these fluctuations prior to catalyzing translocation to form the posttranslocation (POST) complex. EF-G dependent translocation from the classical PRE complex proceeds via transient formation of a short-lived hybrid intermediate. A-site binding of either EF-G to the PRE complex or of aminoacyl-tRNA⋅EF-Tu ternary complex to the POST complex markedly suppresses ribosome conformational lability. PMID:21549313

  2. 188Re-labelled anti-CD20 monoclonal antibody: Labelling and quality control studies

    International Nuclear Information System (INIS)

    Immunotherapy with human chimeric antibody rituximab (Rituxan, IDEC pharmaceuticals) has been a major advance in treatments of patients with CD20-positive B-cell non Hodgkin's lymphoma (NHL). Radioimmunotherapy (RIT) uses the targeting features of monoclonal antibody to deliver radiation from an attached readionuclide and it is an appeling concept that has received widespread attention. Here, we report our experience using rhenium-188 (188Re)- radiolabeled chimeric anti-CD20 antibody (rituximab). A stable antibody-labeling technique had been developed for 188Re. The 188Re-direct labeling of anti-CD20 monoclonal antibody, the methods for quality control: paper chromatography, instant thin layer chromatographysilica gel (ITLC-SG) and HPLC technique, the immunoreactivity and biological recognition of the target antigen assessment of the radiolabeled molecule, in vitro stability and the assessment of in vivo stability through biodistribution studies in normal WISTAR rats are described. For the direct radiolabeling, the reduction of monoclonal antibody (mAb) was performed with 2-mercaptoethanol (2-ME), based on Schwarz's method at a molar ratio 2000:1 (2- ME:mAb). By means of this method some of the disulfide bonds of the antibody are reduced to sulfhydryl groups (we obtained 4-5 groups) and these groups provide sites for the formation of very strong bond between the reduced rhenium and the antibody. The methodology used in this work has been tested in a phase I radioimmunotherapy clinical trial using the humanized mAb hR3 for loco-regional treatment of brain tumours. The labeling efficiency (> 95 %) of this method showed that the final product needs no further purification for clinical purposes (low level formation of colloidal species). In vitro stability studies of the labeled anti-CD20 were performed at room temperature at 4 h, 24 h and 48 h in cysteine, human serum and saline. In the presence of normal human serum, during the first 4h, transchelation of about 15

  3. Improving Recurrent Neural Networks For Sequence Labelling

    OpenAIRE

    Dinarelli, Marco; Tellier, Isabelle

    2016-01-01

    In this paper we study different types of Recurrent Neural Networks (RNN) for sequence labeling tasks. We propose two new variants of RNNs integrating improvements for sequence labeling, and we compare them to the more traditional Elman and Jordan RNNs. We compare all models, either traditional or new, on four distinct tasks of sequence labeling: two on Spoken Language Understanding (ATIS and MEDIA); and two of POS tagging for the French Treebank (FTB) and the Penn Treebank (PTB) corpora. The...

  4. Alternative ways for private label manufacturing

    OpenAIRE

    Kelemen, Zita; Némethné Tömő, Zsuzsa

    2010-01-01

    Private labels are a growing phenomenon globaly. retatlers become stronger and stronger by offering their own quality private label product for customers in all segments. Certainly they do not open factories to produce these items but rather search for dedicated private label producers or pressure branded goods manufacturers to produce it for them. The article deals with the strategic choiches manufacturers can have and suggest the necessary factors that need to be evaluated to decide on the ...

  5. Synthesis of carboxy-labelled 1-carnitine

    Energy Technology Data Exchange (ETDEWEB)

    Goodfellow, D.B.; Hoppel, C.L.; Turkaly, J.S. (Case Western Reserve Univ., Cleveland, OH (USA). School of Medicine)

    1982-03-01

    A method for the production of carboxy-labelled l-carnitine is described. The first step is the chemical synthesis of 4-N-trimethylammoniobutanoate (butyrobetaine) from the precursors 4-aminobutanoate and iodomethane. The second step involves the hydroxylation of butyrobetaine to form l-carnitine using butyrobetaine hydroxylase partially purified from bovine calf liver. The method also can be used to synthesize Me-labelled and uniformly-chain-labelled l-carnitine.

  6. Synthesis of carboxy-labelled 1-carnitine

    International Nuclear Information System (INIS)

    A method for the production of carboxy-labelled l-carnitine is described. The first step is the chemical synthesis of 4-N-trimethylammoniobutanoate (butyrobetaine) from the precursors 4-aminobutanoate and iodomethane. The second step involves the hydroxylation of butyrobetaine to form l-carnitine using butyrobetaine hydroxylase partially purified from bovine calf liver. The method also can be used to synthesize Me-labelled and uniformly-chain-labelled l-carnitine. (author)

  7. Applications of radioactively labelled nucleic acid probes

    International Nuclear Information System (INIS)

    Isotopically labelled nucleic acid probes are used extensively in many areas of molecular biology research. Several radioactive isotopes have been utilised for this purpose, with P-32 and S-35 proving the most popular. This contribution will highlight the factors dictating the choice of radioisotope and will describe techniques for in vitro labelling of nucleic acids. The experimental data presented will be focused on applications of labelled nucleic acids including DNA probe assays and DNA sequencing. (author). 9 refs., 2 figs., 4 tabs

  8. ML-MG: Multi-label Learning with Missing Labels Using a Mixed Graph

    KAUST Repository

    Wu, Baoyuan

    2015-12-07

    This work focuses on the problem of multi-label learning with missing labels (MLML), which aims to label each test instance with multiple class labels given training instances that have an incomplete/partial set of these labels (i.e. some of their labels are missing). To handle missing labels, we propose a unified model of label dependencies by constructing a mixed graph, which jointly incorporates (i) instance-level similarity and class co-occurrence as undirected edges and (ii) semantic label hierarchy as directed edges. Unlike most MLML methods, We formulate this learning problem transductively as a convex quadratic matrix optimization problem that encourages training label consistency and encodes both types of label dependencies (i.e. undirected and directed edges) using quadratic terms and hard linear constraints. The alternating direction method of multipliers (ADMM) can be used to exactly and efficiently solve this problem. To evaluate our proposed method, we consider two popular applications (image and video annotation), where the label hierarchy can be derived from Wordnet. Experimental results show that our method achieves a significant improvement over state-of-the-art methods in performance and robustness to missing labels.

  9. Electron Collisions with Large Molecules

    Science.gov (United States)

    McKoy, Vincent

    2006-10-01

    In recent years, interest in electron-molecule collisions has increasingly shifted to large molecules. Applications within the semiconductor industry, for example, require electron collision data for molecules such as perfluorocyclobutane, while almost all biological applications involve macromolecules such as DNA. A significant development in recent years has been the realization that slow electrons can directly damage DNA. This discovery has spurred studies of low-energy collisions with the constituents of DNA, including the bases, deoxyribose, the phosphate, and larger moieties assembled from them. In semiconductor applications, a key goal is development of electron cross section sets for plasma chemistry modeling, while biological studies are largely focused on understanding the role of localized resonances in inducing DNA strand breaks. Accurate calculations of low-energy electron collisions with polyatomic molecules are computationally demanding because of the low symmetry and inherent many-electron nature of the problem; moreover, the computational requirements scale rapidly with the size of the molecule. To pursue such studies, we have adapted our computational procedure, known as the Schwinger multichannel method, to run efficiently on highly parallel computers. In this talk, we will present some of our recent results for fluorocarbon etchants used in the semiconductor industry and for constituents of DNA and RNA. In collaboration with Carl Winstead, California Institute of Technology.

  10. Classifier Risk Estimation under Limited Labeling Resources

    OpenAIRE

    Kumar, Anurag; Raj, Bhiksha

    2016-01-01

    In this paper we propose strategies for estimating performance of a classifier when labels cannot be obtained for the whole test set. The number of test instances which can be labeled is very small compared to the whole test data size. The goal then is to obtain a precise estimate of classifier performance using as little labeling resource as possible. Specifically, we try to answer, how to select a subset of the large test set for labeling such that the performance of a classifier estimated ...

  11. Novel Properties of Fuzzy Labeling Graphs

    OpenAIRE

    Nagoor Gani, A.; Muhammad Akram; D. Rajalaxmi (a) Subahashini

    2014-01-01

    The concepts of fuzzy labeling and fuzzy magic labeling graph are introduced. Fuzzy magic labeling for some graphs like path, cycle, and star graph is defined. It is proved that every fuzzy magic graph is a fuzzy labeling graph, but the converse is not true. We have shown that the removal of a fuzzy bridge from a fuzzy magic cycle with odd nodes reduces the strength of a fuzzy magic cycle. Some properties related to fuzzy bridge and fuzzy cut node have also been discussed.

  12. Simultaneous segmentation and statistical label fusion

    Science.gov (United States)

    Asman, Andrew J.; Landman, Bennett A.

    2012-02-01

    Labeling or segmentation of structures of interest in medical imaging plays an essential role in both clinical and scientific understanding. Two of the common techniques to obtain these labels are through either fully automated segmentation or through multi-atlas based segmentation and label fusion. Fully automated techniques often result in highly accurate segmentations but lack the robustness to be viable in many cases. On the other hand, label fusion techniques are often extremely robust, but lack the accuracy of automated algorithms for specific classes of problems. Herein, we propose to perform simultaneous automated segmentation and statistical label fusion through the reformulation of a generative model to include a linkage structure that explicitly estimates the complex global relationships between labels and intensities. These relationships are inferred from the atlas labels and intensities and applied to the target using a non-parametric approach. The novelty of this approach lies in the combination of previously exclusive techniques and attempts to combine the accuracy benefits of automated segmentation with the robustness of a multi-atlas based approach. The accuracy benefits of this simultaneous approach are assessed using a multi-label multi-atlas whole-brain segmentation experiment and the segmentation of the highly variable thyroid on computed tomography images. The results demonstrate that this technique has major benefits for certain types of problems and has the potential to provide a paradigm shift in which the lines between statistical label fusion and automated segmentation are dramatically blurred.

  13. Synthesis of tritium labelled 24-epibrassinolide

    Energy Technology Data Exchange (ETDEWEB)

    Kolbe, A.; Marquardt, V.; Adam, G. (Inst. of Plant Biochemistry Halle, Halle/Saale (Germany))

    1992-10-01

    Deuterium and tritium 5,7,7-tris-labelled 24-epibrassinolide were prepared by base catalyzed exchange reaction using 24-epicastasterone tetraacetate 1 or bis-isopropylidenedioxy-24-epicastasterone 8 and labelled water. Baeyer-Villiger oxidation of the obtained labelled 6-ketones 2 and 3 with CF[sub 3]CO[sub 3]H gave after alkaline deacetylation of the resulting 4 and 5 the desired tris-labelled 24-epibrassinolides 6 and 7, respectively, or starting from 9 under simultaneous oxidation and deprotection in one step the same final products. (author).

  14. (d,1)-total labelling of graphs

    OpenAIRE

    Havet, Frédéric; Yu, Min-Li

    2002-01-01

    A $(d,1)$-total labelling of a graph $G$ is an assignment of integers to $V(G)\\cup E(G)$ such that: (i) any two adjacent vertices of $G$ receive distinct integers, (ii) any two adjacent edges of $G$ receive distinct integers, and (iii) a vertex and its incident edge receive integers that differ by at least $d$ in absolute value. The {\\it span} of a $(d,1)$-total labelling is the maximum difference between two labels. The minimum span of a $(d,1)$-total labelling of $G$ is denoted by $\\lambda_...

  15. Radioactivity measuring system of labelled biopolymers

    International Nuclear Information System (INIS)

    System for determining the radioactivity of labelled biopolymers, comprising a bank of containers filled with aqueous solutions of biological samples containing biopolymers. This system features an electric drive to move the bank of containers step by step; a device for the acid precipitation of the biopolymers which sends determined amounts of co-precipitant and diatom suspension in an acid solution to the containers containing a biological sample; a system for taking precipitated samples from the containers; a system for filtering the precipitated biopolymers carrying out successive filterings; placing the deposit into suspension; dissolving the biopolymers and sending the labelled mixture labelled by the scintillation labeller to the detection chamber

  16. Extending Modal Transition Systems with Structured Labels

    DEFF Research Database (Denmark)

    Bauer, Sebastian S.; Juhl, Line; Larsen, Kim Guldstrand; Legay, Axel; Srba, Jiri

    2012-01-01

    We introduce a novel formalism of label-structured modal transition systems that combines the classical may/must modalities on transitions with structured labels that represent quantitative aspects of the model. On the one hand, the specification formalism is general enough to include models like...... weighted modal transition systems and allows the system developers to employ more complex label refinement than in the previously studied theories. On the other hand, the formalism maintains the desirable properties required by any specification theory supporting compositional reasoning. In particular, we...... study modal and thorough refinement, determinization, parallel composition, conjunction, quotient, and logical characterization of label-structured modal transition systems....

  17. Stable isotope labeled L-tryptophan

    International Nuclear Information System (INIS)

    Stable isotope labeled L-tryptophan is an application of nucleus technology in amino acids. Progresses in stable isotope labeled L-tryptophan in recent years are reviewed.. In the respect of synthesis, in addition to the methods of organic synthesis and isotope exchange, the microbial technology which has the advantage of U-label and construct has been used widely. In the respect of applications, stable isotope labeled L-tryptophan as trace has been used widely in yields of medicine, biology and chemistry et al. Along with the development of protein engineering, molecular biology and peptide drugs, they will have a fine future. (authors)

  18. Visualizing repetitive diffusion activity of double-strand RNA binding proteins by single molecule fluorescence assays.

    Science.gov (United States)

    Koh, Hye Ran; Wang, Xinlei; Myong, Sua

    2016-08-01

    TRBP, one of double strand RNA binding proteins (dsRBPs), is an essential cofactor of Dicer in the RNA interference pathway. Previously we reported that TRBP exhibits repetitive diffusion activity on double strand (ds)RNA in an ATP independent manner. In the TRBP-Dicer complex, the diffusion mobility of TRBP facilitates Dicer-mediated RNA cleavage. Such repetitive diffusion of dsRBPs on a nucleic acid at the nanometer scale can be appropriately captured by several single molecule detection techniques. Here, we provide a step-by-step guide to four different single molecule fluorescence assays by which the diffusion activity of dsRBPs on dsRNA can be detected. One color assay, termed protein induced fluorescence enhancement enables detection of unlabeled protein binding and diffusion on a singly labeled RNA. Two-color Fluorescence Resonance Energy Transfer (FRET) in which labeled dsRBPs is applied to labeled RNA, allows for probing the motion of protein along the RNA axis. Three color FRET reports on the diffusion movement of dsRBPs from one to the other end of RNA. The single molecule pull down assay provides an opportunity to collect dsRBPs from mammalian cells and examine the protein-RNA interaction at single molecule platform. PMID:27012177

  19. Laser spectroscopy of cold molecules

    CERN Document Server

    Borri, Simone

    2016-01-01

    This paper reviews the recent results in high-resolution spectroscopy on cold molecules. Laser spectroscopy of cold molecules addresses issues of symmetry violation, like in the search for the electric dipole moment of the electron and the studies on energy differences in enantiomers of chiral species; tries to improve the precision to which fundamental physical constants are known and tests for their possible variation in time and space; tests quantum electrodynamics, and searches for a fifth force. Further, we briefly review the recent technological progresses in the fields of cold molecules and mid-infrared lasers, which are the tools that mainly set the limits for the resolution that is currently attainable in the measurements.

  20. Current-voltage characteristics of single-molecule diarylethene junctions measured with adjustable gold electrodes in solution

    OpenAIRE

    Briechle, Bernd M; Youngsang Kim; Philipp Ehrenreich; Artur Erbe; Dmytro Sysoiev; Thomas Huhn; Ulrich Groth; Elke Scheer

    2012-01-01

    We report on an experimental analysis of the charge transport through sulfur-free photochromic molecular junctions. The conductance of individual molecules contacted with gold electrodes and the current–voltage characteristics of these junctions are measured in a mechanically controlled break-junction system at room temperature and in liquid environment. We compare the transport properties of a series of molecules, labeled TSC, MN, and 4Py, with the same switching core but varying side-...

  1. Free-solution, label-free molecular interactions studied by back-scattering interferometry

    DEFF Research Database (Denmark)

    Bornhop, D.J.; Latham, J.C.; Kussrow, A.;

    2007-01-01

    Free-solution, label-free molecular interactions were investigated with back-scattering interferometry in a simple optical train composed of a helium-neon laser, a microfluidic channel, and a position sensor. Molecular binding interactions between proteins, ions and protein, and small molecules and......, interleukin-2 with its monoclonal antibody, and calmodulin with calcium ion Ca2+, a small molecule inhibitor, the protein calcineurin, and the M13 peptide. The high sensitivity of back-scattering interferometry and small volumes of microfluidics allowed the entire calmodulin assay to be performed with 200...

  2. Differential membrane proteomics using 18O-labeling to identify biomarkers for cholangiocarcinoma

    DEFF Research Database (Denmark)

    Kristiansen, Troels Zakarias; Harsha, H C; Grønborg, Mads; Maitra, Anirban; Pandey, Akhilesh

    2008-01-01

    enrichment of cellular subproteomes prior to mass spectrometric analysis can provide increased coverage of certain classes of molecules. We used a membrane protein enrichment strategy coupled with 18O labeling based quantitative proteomics to identify proteins that are highly expressed in cholangiocarcinomas....... In addition to identifying several proteins previously known to be overexpressed in cholangiocarcinoma, we discovered a number of molecules that were previously not associated with cholangiocarcinoma. Using immunoblotting and immunohistochemical labeling of tissue microarrays, we validated Golgi...... membrane protein 1, Annexin IV and Epidermal growth factor receptor pathway substrate 8 (EPS8) as candidate biomarkers for cholangiocarcinomas. Golgi membrane protein 1 was observed to be overexpressed in 89% of cholangiocarcinoma cases analyzed by staining tissue microarrays. In light of recent reports...

  3. Synthesis and labelling of epidepride

    International Nuclear Information System (INIS)

    S-(-)-N-[(1-ethyl-2-pyrrolidinyl) methyl]-5-iodo-2,3-dimethoxybenzamide (proposed generic name, epidepride) is a very potent dopamine D2 antagonist. It was synthesized by five steps from 3-methoxysalicylic acid. [131I]epidepride was obtained in 97.3% radiochemical yields from the corresponding 5-(tributyltin) derivative using hydrogen peroxide as the oxidant. The aryltin precursor was prepared from non-labelled epidepride by palladium-catalyzed stannylene using bis (tri-n-butyltin) in triethylamine. [131I] epidepride was stable under 4 degree C, and partition coefficient was 72.3 at pH 7.40. The biodistribution study in rats exhibited high localization in the striatum of the brain with the striatum/cerebellum ratio reaching 237/1 at 320 min postinjection. All these results suggest that [131I] epidepride may be used widely as a useful dopamine D2 receptor imaging agent for SPECT

  4. Synthesis and labelling of epidepride

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    S-(-)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenzamide (proposed generic name, epidepride) is a very potent dopamine D2 antagonist. It was synthesized by five steps from 3-methoxysalicylic acid. [131I]epidepride was obtained in 97.3% radiochemical yields from the corresponding 5-(tributyltin) derivative using hydrogen peroxide as the oxidant. The aryltin precursor was prepared from non-labelled epidepride by palladium-catalyzed stannylation using bis(tri-n-butyltin) in triethylamine. [131I]epidepride was stable under 4℃, and partition coefficient was 72.3 at pH 7.40. The biodistribution study in rats exihibited high localization in the striatum of the brain with the striatum/cerebellum ratio reaching 237/1 at 320 min postinjection.All these results suggest that[131I]epidepride may be usedd widely as a useful dopamineD2 receptor imaging agent for SPECT.

  5. Principles of food product labelling

    Directory of Open Access Journals (Sweden)

    Krystyna Krysztofiak

    2011-09-01

    Full Text Available The purpose of the label of the food product is to provide information on ingredients and additionally on its origin, production method, storage conditions, date tagging, as well as to enable to identify the producer or distributor of this product. Legal regulations precisely give instructions on the range and the way of the presentation of these data, so they could be clear and understandable for the average consumer. Since 25th of November 2005, the information about allergens’ presence must be placed on the label, regardless of their content in the product (Directive 2003/89/WE... 2003 – Off. J. L 308: 15-18. The Regulation (WE No 1924/2006 about placing the nutritional information and medicinal claims concerning foods (Regulation (WE No 1924/2006... 2006 a is valid in all countries of European Union since 1st of July 2007 (Off. J. L 404: 9-25. It coordinates the legislative, executive and administrative regulations connected with this labelling. According to these regulations, “nutritional information” states, suggests or gives to understand that the food product has special properties concerning its ingredients. Those statements are of type: “the source of...”, “no... content”, “high content of...”, “low content of...”, “reduced content of...” with reference to calorie or selected ingredients’ content. “Medicinal claims” state, suggest or give to understand, that there is a connection between the food product or one of its ingredients and the health condition of the consumer. First type of these medicinal claims refers to the influence of the ingredient on the physiology. Such a statement is based on generally accepted scientific conclusions and could be properly understood by the average consumer, e.g. “calcium takes part in the process of building of strong bones”. “Statements about decreasing the risk of a disease” give information, that food product or one of its ingredients efficiently

  6. Technetium-aspirin molecule complexes

    International Nuclear Information System (INIS)

    Technetium-aspirin and technetium-aspirin-like molecule complexes were prepared. The structure of N-acetylanthranilic acid (NAA) has been decided through CNDO calculations. The ionization potential and electron affinity of the NAA molecule as well as the charge densities were calculated. The electronic absorption spectra of Tc(V)-Asp and Tc(V)-ATS complexes have two characteristic absorption bands at 450 and 600 nm, but the Tc(V)-NAA spectrum has one characteristic band at 450 nm. As a comparative study, Mo-ATS complex was prepared and its electronic absorption spectrum is comparable with the Tc-ATS complex spectrum. (author)

  7. Phase structure of soliton molecules

    International Nuclear Information System (INIS)

    Temporal optical soliton molecules were recently demonstrated; they potentially allow further increase of data rates in optical telecommunication. Their binding mechanism relies on the internal phases, but these have not been experimentally accessible so far. Conventional frequency-resolved optical gating techniques are not suited for measurement of their phase profile: Their algorithms fail to converge due to zeros both in their temporal and their spectral profile. We show that the VAMPIRE (very advanced method of phase and intensity retrieval of E-fields) method performs reliably. With VAMPIRE the phase profile of soliton molecules has been measured, and further insight into the mechanism is obtained

  8. Phase structure of soliton molecules

    Science.gov (United States)

    Hause, A.; Hartwig, H.; Seifert, B.; Stolz, H.; Böhm, M.; Mitschke, F.

    2007-06-01

    Temporal optical soliton molecules were recently demonstrated; they potentially allow further increase of data rates in optical telecommunication. Their binding mechanism relies on the internal phases, but these have not been experimentally accessible so far. Conventional frequency-resolved optical gating techniques are not suited for measurement of their phase profile: Their algorithms fail to converge due to zeros both in their temporal and their spectral profile. We show that the VAMPIRE (very advanced method of phase and intensity retrieval of E -fields) method performs reliably. With VAMPIRE the phase profile of soliton molecules has been measured, and further insight into the mechanism is obtained.

  9. Orbital molecules in electronic materials

    Energy Technology Data Exchange (ETDEWEB)

    Attfield, J. Paul, E-mail: j.p.attfield@ed.ac.uk [Centre for Science at Extreme Conditions and School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JZ (United Kingdom)

    2015-04-01

    Orbital molecules are made up of coupled orbital states on several metal ions within an orbitally ordered (and sometimes also charge-ordered) solid such as a transition metal oxide. Spin-singlet dimers are known in many materials, but recent discoveries of more exotic species such as 18-electron heptamers in AlV{sub 2}O{sub 4} and magnetic 3-atom trimerons in magnetite (Fe{sub 3}O{sub 4}) have shown that orbital molecules constitute a general new class of quantum electronic states in solids.

  10. Recoiling DNA Molecule Simulation & Experiment

    CERN Document Server

    Neto, J C; Mesquita, O N; Neto, Jose Coelho; Dickman, Ronald

    2002-01-01

    Many recent experiments with single DNA molecules are based on force versus extension measurements and involve tethering a microsphere to one of its extremities and the other to a microscope coverglass. In this work we show that similar results can also be obtained by studying the recoil dynamics of the tethered microspheres. Computer simulations of the corresponding Langevin equation indicate which assumptions are required for a reliable analysis of the experimental recoil curves. We have measured the persistence length A of single naked DNA molecules and DNA-Ethidium Bromide complexes using this approach.

  11. Teaching lasers to control molecules

    International Nuclear Information System (INIS)

    We simulate a method to teach a laser pulse sequences to excite specified molecular states. We use a learning procedure to direct the production of pulses based on ''fitness'' information provided by a laboratory measurement device. Over a series of pulses the algorithm learns an optimal sequence. The experimental apparatus, which consists of a laser, a sample of molecules and a measurement device, acts as an analog computer that solves Schroedinger's equation n/Iexactly, in real time. We simulate an apparatus that learns to excite specified rotational states in a diatomic molecule

  12. A general method for the production of 125I-labelled low-molecular-weight tracers for radioimmunoassay

    International Nuclear Information System (INIS)

    A general method is described for the separation of low-molecular-weight 125I-labelled tracers from a chloramine-T labelling mixture, containing the starting material, the tracer, labelled by-products, free radioiodine and reagents used in the labelling procedure. Small molecules like tyrosine, thyronine and steroids as well as their tyrosine methyl ester conjugates are adsorbed on Sephadex LH-20 dextran gel. The introduction of iodine atoms increases the elution volume and the distribution coefficient in proportion to the number of iodine atoms per molecule. Organic solvents like ethanol are also adsorbed on dextran gel, which results in desorption of the starting material or its iodine-substituted derivatives. The elution order follows the number of iodine substituents per molecule, i.e. unsubstituted starting material, mono-, di-, tri- and tetra-substituted molecules. Using a water/ethanol binary eluent in which water can be considered as inert diluent, the elution is governed by the ethanol concentration. The finding that the logarithm of the distribution coefficient of the solutes is linearly correlated with the logarithm of the ethanol concentration permits an optimization of the separation. (author)

  13. Perceived barriers and motives to reading nutrition label among label ‘non-users’ in Croatia

    OpenAIRE

    Ranilović, Jasmina; Colić Barić, Irena

    2013-01-01

    The purpose of this paper is to examine barriers and motives associated with reading nutrition information among label ‘non-users’ in Croatia and relationship with demographic and health factors of recruited sample.Label ‘non-users’ are subjects reported that had never or do not know or wish to tell aboutreading nutrition label during food purchasing (n=375) and were recruited from representative sample telephone interviewed Croatian, for assessing nutrition label attitudes. It is found that ...

  14. Characterizing Active Pharmaceutical Ingredient Binding to Human Serum Albumin by Spin-Labeling and EPR Spectroscopy.

    Science.gov (United States)

    Hauenschild, Till; Reichenwallner, Jörg; Enkelmann, Volker; Hinderberger, Dariush

    2016-08-26

    Drug binding to human serum albumin (HSA) has been characterized by a spin-labeling and continuous-wave (CW) EPR spectroscopic approach. Specifically, the contribution of functional groups (FGs) in a compound on its albumin-binding capabilities is quantitatively described. Molecules from different drug classes are labeled with EPR-active nitroxide radicals (spin-labeled pharmaceuticals (SLPs)) and in a screening approach CW-EPR spectroscopy is used to investigate HSA binding under physiological conditions and at varying ratios of SLP to protein. Spectral simulations of the CW-EPR spectra allow extraction of association constants (KA ) and the maximum number (n) of binding sites per protein. By comparison of data from 23 SLPs, the mechanisms of drug-protein association and the impact of chemical modifications at individual positions on drug uptake can be rationalized. Furthermore, new drug modifications with predictable protein binding tendency may be envisaged. PMID:27460503

  15. Use of deuterium labelled glucose in evaluating the pathway of hepatic glycogen synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, M.N.; Masuoka, L.K.; deRopp, J.S.; Jones, A.D.

    1989-03-15

    Deuterium labelled glucose has been used to study the pathway of hepatic glycogen synthesis during the fasted-refed transition in rats. Deuterium enrichment of liver glycogen was determined using nuclear magnetic resonance as well as mass spectroscopy. Sixty minutes after oral administration of deuterated glucose to fasted rats, the portal vein blood was fully enriched with deuterated glucose. Despite this, less than half of the glucose molecules incorporated into liver glycogen contained deuterium. The loss of deuterium label from glucose is consistent with hepatic glycogen synthesis by an indirect pathway requiring prior metabolism of glucose. The use of deuterium labelled glucose may prove to be a useful probe to study hepatic glycogen metabolism. Its use may also find application in the study of liver glycogen metabolism in humans by a noninvasive means.

  16. Synthesis of carbon-11, fluorine-18, and nitrogen-13 labeled radiotracers for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Wolf, A.P.

    1981-01-01

    A number of reviews, many of them recent, have appeared on various aspects of /sup 11/C, /sup 18/F and /sup 13/N-labeled radiotracers. This monograph treats the topic principally from the standpoint of synthetic organic chemistry while keeping in perspective the necessity of integrating the organic chemistry with the design and ultimate application of the radiotracer. Where possible, recent examples from the literature of organic synthesis are introduced to suggest potentially new routes which may be applied to problems in labeling organic molecules with the short-lived positron emitters, carbon-11, fluorine-18, and nitrogen-13. The literature survey of carbon-11, fluorine-18 and nitrogen-13 labeled compounds presented are of particular value to scientists working in this field. Two appendices are also included to provide supplementary general references. A subject index concludes this volume.

  17. Horseradish peroxidase-driven fluorescent labeling of nanotubes with quantum dots.

    Science.gov (United States)

    Didenko, Vladimir V; Baskin, David S

    2006-03-01

    We describe the first enzyme-driven technique for fluorescent labeling of single-walled carbon nanotubes (SWNTs). The labeling was performed via enzymatic biotinylation of nanotubes in the tyramide-horseradish peroxidase (HRP) reaction. Both direct and indirect fuorescent labeling of SWNTs was achieved using either biotinyl tyramide or fluorescently tagged tyramides. Biotinylated SWNTs later reacted with streptavidin-conjugated fluorophores. Linking semiconductor nanocrystals, quantum dots (Q-dots), to the surface of nanotubes resulted in their fluorescent visualization, whereas conventional fluorophores bound to SWNTs directly or through biotin-streptavidin linkage, were completely quenched. Enzymatic biotinylation permits fluorescent visualization of carbon nanotubes, which could be useful for a number of biomedical applications. In addition, other organic molecules such as proteins, antibodies, or DNA can be conjugated to biotinylated SWNTs using this approach. PMID:16568818

  18. Synthesis of carbon-11, fluorine-18, and nitrogen-13 labeled radiotracers for biomedical applications

    International Nuclear Information System (INIS)

    A number of reviews, many of them recent, have appeared on various aspects of 11C, 18F and 13N-labeled radiotracers. This monograph treats the topic principally from the standpoint of synthetic organic chemistry while keeping in perspective the necessity of integrating the organic chemistry with the design and ultimate application of the radiotracer. Where possible, recent examples from the literature of organic synthesis are introduced to suggest potentially new routes which may be applied to problems in labeling organic molecules with the short-lived positron emitters, carbon-11, fluorine-18, and nitrogen-13. The literature survey of carbon-11, fluorine-18 and nitrogen-13 labeled compounds presented are of particular value to scientists working in this field. Two appendices are also included to provide supplementary general references. A subject index concludes this volume

  19. A new method for tritium labelling of neuraminidase from Vibrio cholerae

    International Nuclear Information System (INIS)

    This research work related to the radioactive labelling with tritium of the enzyme neuraminidase from Vibrio cholerae by an easily handled method. The reactive compound N-propionyloxysuccinimide, the ester of propionic acid and N-hydroxysuccinimide, offered a suitable labelling reagent. For comparison purposes an already known method of labelling neuraminidase with tritium by the oxidation of hydroxyl groups of the hydrocarbon chain of the enzymal protein and subsequent reduction of the aldehyde groups formed with tritiated sodium borhydride, was also carried out. The advantages and disadvantages of both methods are described in detail, in particular with regard to yields of radioactivity and the influence on enzyme activity. The fact that only 1 mg enzymal protein was available for each modification of the enzyme molecule posed particular problems and, as a consequence, extensive preliminary experiments had to be carried with another protein (beef serum album) in the same concentration range. (orig./MG)

  20. Exotic helium molecules; Molecules exotiques d'helium

    Energy Technology Data Exchange (ETDEWEB)

    Portier, M

    2007-12-15

    We study the photo-association of an ultracold cloud of magnetically trapped helium atoms: pairs of colliding atoms interact with one or two laser fields to produce a purely long range {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}P{sub 0}) molecule, or a {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}S{sub 1}) long range molecule. Light shifts in one photon photo-association spectra are measured and studied as a function of the laser polarization and intensity, and the vibrational state of the excited molecule. They result from the light-induced coupling between the excited molecule, and bound and scattering states of the interaction between two metastable atoms. Their analysis leads to the determination of the scattering length a = (7.2 {+-} 0.6) ruling collisions between spin polarized atoms. The two photon photo-association spectra show evidence of the production of polarized, long-range {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}S{sub 1}) molecules. They are said to be exotic as they are made of two metastable atoms, each one carrying a enough energy to ionize the other. The corresponding lineshapes are calculated and decomposed in sums and products of Breit-Wigner and Fano profiles associated to one and two photon processes. The experimental spectra are fit, and an intrinsic lifetime {tau} = (1.4 {+-} 0.3) {mu}s is deduced. It is checked whether this lifetime could be limited by spin-dipole induced Penning autoionization. This interpretation requires that there is a quasi-bound state close to the dissociation threshold in the singlet interaction potential between metastable helium atoms for the theory to match the experiment. (author)

  1. Synthesis of water-dispersible zinc oxide quantum dots with antibacterial activity and low cytotoxicity for cell labeling

    International Nuclear Information System (INIS)

    Typical photoluminescent semiconductor nanoparticles, called quantum dots (QDs), have potential applications in biological labeling. When used to label stem cells, QDs may impair the differentiation capacity of the stem cells. In this study, we synthesized zinc oxide (ZnO) QDs in methanol with an average size of ∼2 nm. We then employed two different types of polyethylene glycol (PEG) molecules (SH-PEG-NH2 and NH2-PEG-NH2) to conjugate ZnO QDs and made them water-dispersible. Fourier transform infrared spectroscopy spectra indicated the attachment of PEG molecules on ZnO QDs. No obvious size alteration was observed for ZnO QDs after PEG conjugation. The water-dispersible ZnO QDs still retained the antibacterial activity and fluorescence intensity. The cytotoxicity evaluation revealed that ZnO QDs at higher concentrations decreased cell viability but were generally safe at 30 ppm or below. Cell lines of hepatocytes (HepG2), osteoblasts (MC3T3-E1) and mesenchymal stem cells (MSCs) were successfully labeled by the water-dispersible ZnO QDs at 30 ppm. The ZnO QD-labeled MSCs maintained their stemness and differentiation capacity. Therefore, we conclude that the water-dispersible ZnO QDs developed in this study have antibacterial activity, low cytotoxicity, and proper labeling efficiency, and can be used to label a variety of cells including stem cells. (paper)

  2. Chain store management through private labels strategy

    Directory of Open Access Journals (Sweden)

    Martina Sopta

    2007-07-01

    Full Text Available The purpose of this paper is to examine the market shares of private labels in the European Union and on the global market, and to compare the results of the analysis with the level of presence of private labels on the Croatian market. Moreover, through the application of macro and microeconomic tools, the author tried to estimate the future trends of private labels in Croatia.For the purpose of the paper secondary and primary data was used in the research. Relevant scientific and professional literature of local and foreign authors was analyzed. In addition, a few recent research studies were analyzed and their results compared. Field research has been conducted by the survey method, with 225 respondents included in the intentional sample.The main hypothesis of the paper based on research is that, in total sales, private labels are gaining a growing share in all markets, regardless of the development level of those markets. Alongside the main hypothesis of the work, three supporting hypotheses were tested to see which private labels are a good alternative to other brands on the world market. Private labels are generally developed on generic products. The third supporting hypothesis starts from the assumption that the investments in the promotion of private labels are negligible, resulting in lower prices of thoseproducts. The results of research and analyses in the work indicate that the position of private labels will strengthen internationally, as part of the process of liberalization and globalization of trade flows. In the process of purchase of private labels the positioning of the point of sale and price have an increasing contribution. With the concentration of commerce in chain stores, the share of private labels grows, approaching a half of the total sales in some countries. Considering the Croatian market, according to the international product life cycle theory, the share of private labels in the total sales will grow in the future

  3. Spatial arrangement of rhodopsin in retinal rod outer segment membranes studied by spin-labeling and pulsed electron double resonance

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Satoshi [Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Department of Space and Earth Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Hara, Hideyuki [Bruker Biospin, Yokohama, Kanagawa 215-0022 (Japan); Tokunaga, Fumio [Department of Space and Earth Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Arata, Toshiaki, E-mail: arata@bio.sci.osaka-u.ac.jp [Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Department of Space and Earth Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Use of spin labeling and PELDOR to measure inter-rhodopsin distance in ROS. Black-Right-Pointing-Pointer Strong decay of PELDOR signal indicated a high density (mM range) of rhodopsin. Black-Right-Pointing-Pointer The decay was modeled by rhodopsin monomers dispersed in a planar membrane. -- Abstract: We have determined the spatial arrangement of rhodopsin in the retinal rod outer segment (ROS) membrane by measuring the distances between rhodopsin molecules in which native cysteines were spin-labeled at {approx}1.0 mol/mol rhodopsin. The echo modulation decay of pulsed electron double resonance (PELDOR) from spin-labeled ROS curved slightly with strong background decay. This indicated that the rhodopsin was densely packed in the retina and that the rhodopsin molecules were not aligned well. The curve was simulated by a model in which rhodopsin is distributed randomly as monomers in a planar membrane.

  4. Expanding the chemical scope of RNA:methyltransferases to site-specific alkynylation of RNA for click labeling

    Science.gov (United States)

    Motorin, Yuri; Burhenne, Jürgen; Teimer, Roman; Koynov, Kaloian; Willnow, Sophie; Weinhold, Elmar; Helm, Mark

    2011-01-01

    This work identifies the combination of enzymatic transfer and click labeling as an efficient method for the site-specific tagging of RNA molecules for biophysical studies. A double-activated analog of the ubiquitous co-substrate S-adenosyl-l-methionine was employed to enzymatically transfer a five carbon chain containing a terminal alkynyl moiety onto RNA. The tRNA:methyltransferase Trm1 transferred the extended alkynyl moiety to its natural target, the N2 of guanosine 26 in tRNAPhe. LC/MS and LC/MS/MS techniques were used to detect and characterize the modified nucleoside as well as its cycloaddition product with a fluorescent azide. The latter resulted from a labeling reaction via Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition click chemistry, producing site-specifically labeled RNA whose suitability for single molecule fluorescence experiments was verified in fluorescence correlation spectroscopy experiments. PMID:21037259

  5. Portion Size Labeling and Intended Soft Drink Consumption: The Impact of Labeling Format and Size Portfolio

    Science.gov (United States)

    Vermeer, Willemijn M.; Steenhuis, Ingrid H. M.; Leeuwis, Franca H.; Bos, Arjan E. R.; de Boer, Michiel; Seidell, Jacob C.

    2010-01-01

    Objective: To assess what portion size labeling "format" is most promising in helping consumers selecting appropriate soft drink sizes, and whether labeling impact depends on the size portfolio. Methods: An experimental study was conducted in fast-food restaurants in which 2 labeling formats (ie, reference portion size and small/medium/large…

  6. To Label or Not to Label: The Special Education Question for African Americans

    Science.gov (United States)

    Gold, Moniqueka E.; Richards, Heraldo

    2012-01-01

    Over the years, the benefits of categorically identifying and labeling students with disabilities have been debated on many grounds, particularly when it comes to labeling African-American children who many argue are over-labeled or disproportionately represented in selected categories such as learning disabilities. In this article, the authors…

  7. Improved Intensity-Based Label-Free Quantification via Proximity-Based Intensity Normalization (PIN)

    OpenAIRE

    Van Riper, Susan K.; de Jong, Ebbing P.; Higgins, LeeAnn; Carlis, John V.; Griffin, Timothy J.

    2014-01-01

    Researchers are increasingly turning to label-free MS1 intensity-based quantification strategies within HPLC–ESI–MS/MS workflows to reveal biological variation at the molecule level. Unfortunately, HPLC–ESI–MS/MS workflows using these strategies produce results with poor repeatability and reproducibility, primarily due to systematic bias and complex variability. While current global normalization strategies can mitigate systematic bias, they fail when faced with complex variability stemming f...

  8. Synthesis of organic substances labelled with 14C and 35S

    International Nuclear Information System (INIS)

    After a brief history of the development of the Section des Molecules marquees of the French Atomic Energy Commission, the author gives an outline of the synthesis of the following labelled compounds: benzene 14C-6; phenyl-p-fluorophenyl, thienyl-2 β alanines β 14C; noradrenaline β 14C (arterenol β 14C), dotriacontane 14C-16-17, aminoethane sulfinic acid (hypotaurine 35S). (author)

  9. Investigation of surface potential asymmetry in phospholipid vesicles by a spin label relaxation method.

    OpenAIRE

    Sundberg, S A; Hubbell, W L

    1986-01-01

    In earlier work, Castle and Hubbell (1976) demonstrated the use of a spin-labeled amphiphile as a probe for the electrostatic potential at the outer surface of charged phospholipid vesicles. In recent experiments, we have shown that the hydrophobic anion tetraphenylboron (TPB) promotes transbilayer migration of the probe molecule. Relaxation data recorded following the rapid mixing of the probe with TPB-containing vesicle samples provides information about the electrostatic potentials at both...

  10. Alexa Fluor-labeled Fluorescent Cellulose Nanocrystals for Bioimaging Solid Cellulose in Spatially Structured Microenvironments

    Energy Technology Data Exchange (ETDEWEB)

    Grate, Jay W.; Mo, Kai-For; Shin, Yongsoon; Vasdekis, Andreas; Warner, Marvin G.; Kelly, Ryan T.; Orr, Galya; Hu, Dehong; Dehoff, Karl J.; Brockman, Fred J.; Wilkins, Michael J.

    2015-03-18

    Cellulose nanocrystal materials have been labeled with modern Alexa Fluor dyes in a process that first links the dye to a cyanuric chloride molecule. Subsequent reaction with cellulose nanocrystals provides dyed solid microcrystalline cellulose material that can be used for bioimaging and suitable for deposition in films and spatially structured microenvironments. It is demonstrated with single molecular fluorescence microscopy that these films are subject to hydrolysis by cellulose enzymes.

  11. Iodine-123-labeled pH shift brain-imaging agents

    International Nuclear Information System (INIS)

    HIPDM is an 123I-labeled agent with a distribution in brain reflecting regional perfusion. This compound is neutral and lipid soluble at blood pH and freely crosses the blood-brain barrier. At the lower pH in brain, it picks up a hydrogen ion and becomes positively charged. In this form the molecule is not lipid soluble and it is trapped in brain

  12. Preparation and use of NHS-MAG3 for technetium-99m labeling of DNA

    International Nuclear Information System (INIS)

    The chelator mercaptoacetylglycylglycylglycine (MAG3) is one of several amidothiols that have been used successfully to radiolabel proteins and other molecules with 99mTc. Prior to radiolabeling, the sulfur in these amidothiols is usually protected by a benzoyl group (i.e. S-benzoyl MAG3) which requires extreme alkaline pH or boiling water temperatures for rapid deprotection. As a result, the benzoyl-protected chelator is radiolabeled prior to conjugation (i.e. preconjugation labeling) in the case of carriers such as proteins or polypeptides which cannot withstand harsh conditions. We have employed a simple, two-step, synthesis of the N-hydroxysuccinimide ester of MAG3 in which the sulfur is protected with an acetyl group (i.e. S-acetyl NHS-MAG3). A single-stranded amine-derivitized DNA was coupled with NHS-S-acetyl MAG3. Radiolabeling was accomplished at room temperature and neutral pH by transchelation from 99mTc-tartrate. In comparison to labeled SHNH-DNA, the labeled MAG3-DNA was unstable to cysteine transchelation, however, in contrast to SHNH-DNA, no evidence for serum protein binding of the labeled MAG3-DNA was observed. We conclude that the S-acetyl NHS MAG3 bifunctional chelator may prove to be an attractive alternative method of radiolabeling DNA and other biologically important molecules with 99mTc

  13. Multiphoton dissociation of polyatomic molecules

    International Nuclear Information System (INIS)

    The dynamics of infrared multiphoton excitation and dissociation of SF6 was investigated under collision free conditions by a crossed laser-molecular beam method. In order to understand the excitation mechanism and to elucidate the requirements of laser intensity and energy fluence, a series of experiments were carried out to measure the dissociation yield dependences on energy fluence, vibrational temperature of SF6, the pulse duration of the CO2 laser and the frequency in both one and two laser experiments. Translational energy distributions of the SF5 dissociation product measured by time of flight and angular distributions and the dissociation lifetime of excited SF6 as inferred from the observation of secondary dissociation of SF5 into SF4 and F during the laser pulse suggest that the dynamics of dissociation of excited molecules is dominated by complete energy randomization and rapid intramolecular energy transfer on a nanosecond timescale, and can be adequately described by RRKM theory. An improved phenomenological model including the initial intensity dependent excitation, a rate equation describing the absorption and stimulated emission of single photons, and the unimolecular dissociation of excited molecules is constructed based on available experimental results. The model shows that the energy fluence of the laser determines the excitation of molecules in the quasi-continuum and the excess energy with which molecules dissociate after the laser pulse. The role played by the laser intensity in multiphoton dissociation is more significant than just that of overcoming the intensity dependent absorption in the lowest levels. 63 references

  14. Tunneling Ionization of Diatomic Molecules

    DEFF Research Database (Denmark)

    Svensmark, Jens Søren Sieg

    2016-01-01

    of tunneling ionizaion of molecules is presented and the results of numerical calculations are shown. One perhaps surprising result is, that the frequently used Born-Oppenheimer approximation breaks down for weak fields when describing tunneling ionization. An analytic theory applicable in the weak...

  15. Monitoring Molecules: Insights and Progress

    OpenAIRE

    Wightman, R Mark

    2014-01-01

    In August, 2014, neuroscientists and physical scientists gathered together on the campus of the University of California, Los Angeles to discuss how to monitor molecules in neuroscience. This field has seen significant growth since its inception in the 1970s. Here, the advances in this field are documented, including its advance into understanding the actions that specific neurotransmitters mediate during behavior.

  16. Azobenzene-functionalized cascade molecules

    DEFF Research Database (Denmark)

    Archut, A.; Vogtle, F.; De Cola, L.;

    1998-01-01

    Cascade molecules bearing up to 32 azobenzene groups in the periphery have been prepared from poly(propylene imine) dendrimers and N-hydroxysuccinimide esters. The dendritic azobenzene species show similar isomerization properties as the corresponding azobenzene monomers. The all-E azobenzene den...

  17. Engineering crystals of dendritic molecules.

    Science.gov (United States)

    Lukin, Oleg; Schubert, Dirk; Müller, Claudia M; Schweizer, W Bernd; Gramlich, Volker; Schneider, Julian; Dolgonos, Grygoriy; Shivanyuk, Alexander

    2009-07-01

    A detailed single-crystal X-ray study of conformationally flexible sulfonimide-based dendritic molecules with systematically varied molecular architectures was undertaken. Thirteen crystal structures reported in this work include 9 structures of the second-generation dendritic sulfonimides decorated with different aryl groups, 2 compounds bearing branches of both second and first generation, and 2 representatives of the first generation. Analysis of the packing patterns of 9 compounds bearing second-generation branches shows that despite their lack of strong directive functional groups there is a repeatedly reproduced intermolecular interaction mode consisting in an anchor-type packing of complementary second-generation branches of neighbouring molecules. The observed interaction tolerates a wide range of substituents in meta- and para-positions of the peripheral arylsulfonyl rings. Quantum chemical calculations of the molecule-molecule interaction energies agree at the qualitative level with the packing preferences found in the crystalline state. The calculations can therefore be used as a tool to rationalize and predict molecular structures with commensurate and non-commensurate branches for programming of different packing modes in crystal. PMID:19549870

  18. Nucleic Acids as Information Molecules.

    Science.gov (United States)

    McInerney, Joseph D.

    1996-01-01

    Presents an activity that aims at enabling students to recognize that DNA and RNA are information molecules whose function is to store, copy, and make available the information in biological systems, without feeling overwhelmed by the specialized vocabulary and the minutia of the central dogma. (JRH)

  19. Quantum interferometry with complex molecules

    OpenAIRE

    Arndt, Markus; Hornberger, Klaus

    2009-01-01

    This chapter reviews recent experiments on matter wave interferometry with large molecules. Starting from an elementary introduction to matter wave physics we discuss far-field diffraction and near-field interferometry with thermally excited many-body systems. We describe the constraints imposed by decoherence and dephasing effects, and present an outlook to the future challenges in macromolecule and cluster interferometry.

  20. Nobel Lecture: Single-molecule spectroscopy, imaging, and photocontrol: Foundations for super-resolution microscopy*

    Science.gov (United States)

    Moerner, W. E. William E.

    2015-10-01

    The initial steps toward optical detection and spectroscopy of single molecules in condensed matter arose out of the study of inhomogeneously broadened optical absorption profiles of molecular impurities in solids at low temperatures. Spectral signatures relating to the fluctuations of the number of molecules in resonance led to the attainment of the single-molecule limit in 1989 using frequency-modulation laser spectroscopy. In the early 1990s, many fascinating physical effects were observed for individual molecules, and the imaging of single molecules as well as observations of spectral diffusion, optical switching and the ability to select different single molecules in the same focal volume simply by tuning the pumping laser frequency provided important forerunners of the later super-resolution microscopy with single molecules. In the room-temperature regime, imaging of single copies of the green fluorescent protein also uncovered surprises, especially the blinking and photoinduced recovery of emitters, which stimulated further development of photoswitchable fluorescent protein labels. Because each single fluorophore acts as a light source roughly 1 nm in size, microscopic observation and localization of individual fluorophores is a key ingredient to imaging beyond the optical diffraction limit. Combining this with active control of the number of emitting molecules in the pumped volume led to the super-resolution imaging of Eric Betzig and others, a new frontier for optical microscopy beyond the diffraction limit. The background leading up to these observations is described and selected current developments are summarized.

  1. Spectroscopic and transport measurements of single molecules in solution using an electrokinetic trap

    Science.gov (United States)

    Wang, Quan; Moerner, W. E.

    2014-03-01

    In aqueous solution, diffusion generally limits the observation window of a nano-meter sized single molecule to milliseconds and prevents quantitative determination of spectroscopic and transport properties molecule-by-molecule. The anti-Brownian electrokinetic (ABEL) trap is a feedback-based microfluidic device that enables prolonged (multiseconds) observation of single molecules in solution. The amount of information that can be extracted from each molecule in solution is thus boosted by three orders of magnitude. We describe recent advances in extending the ABEL trap to conduct both spectroscopic and transport measurements of single trapped molecules. First, by combining the trap with multi-parameter fluorescence detection, synchronized dynamics in different observables can be visualized in solution. We use single molecules of Atto 633 as an example and show that this popular label switches between different emissive states under common imaging conditions. Next, we show how transport properties of trapped single molecules can be extracted in addition to spectroscopic readouts. Due to their direct sensitivity to molecular size and charge, measured transport coefficients can be used to distinguish different molecular species and trace biomolecular interactions in solution. We demonstrate this new paradigm by monitoring DNA hybridization/melting in real-time.

  2. On the Complexity of Labeled Oriented Trees

    Indian Academy of Sciences (India)

    Stephan Rosebrock

    2010-02-01

    We define a notion of complexity for labeled oriented trees (LOTs) related to the bridge number in knot theory and prove that LOTs of complexity 2 are aspherical. We also present a class of LOTs of higher complexity which is aspherical, give an upper bound for the complexity of labeled oriented intervals and study the complexity of torus knots.

  3. China Cotton label to be generalized

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    "China Cotton"authorization press conference was held in Beijing on October 11. China Cotton Association granted authorization to the first four enterprises, allowing them to use the label of China Cotton on their qualified products. Shandong Lanyan Group, Beijing Miantian Textile Co., Ltd are among the fi rst companies authorized to use China Cotton label.

  4. Eco-Labeling Perspectives amongst Malaysian Consumers

    Directory of Open Access Journals (Sweden)

    Nik Ramli Nik Abdul Rashid

    2009-04-01

    Full Text Available This study explores the Malaysian consumers’ trust of an eco-label and the influence it has in their choice for the corresponding environment friendly product. Taking into consideration the infancy stage of the Malaysia green marketing initiative, traditional approach to evaluating local consumer receptiveness to the eco-label might not be suitable. This paper approaches the introduction of eco-label with two perspectives in mind. Firstly, while earlier studies from the western scholars use eco-label as a part of the augmented product, this study introduces eco-label as a separate moderating variable. Secondly, the choice of employees working in ISO14001 certified organizations as the population explore a potentially conducive place to initiate a systematic effort in developing a green consumer community. The result is very encouraging. This study has shown that, with some exposure to environmental related experiences Malaysian consumer would indeed react positively to the eco-label. In fact, for situation that requires them to consider environmental aspects of a product that they wish to purchase, the eco-label will definitely be the crucial factor that will push them to make the right purchase choice. Key words: Eco-label; Environmental attitude; Knowledge of Environmental Issues; Green Products; Environmental Management System

  5. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... Lessons? Visit KidsHealth in the Classroom What Other Parents Are Reading Upsetting News Reports? What to Say ... Read a Nutrition Facts Label (Video) KidsHealth > For Parents > How to Read a Nutrition Facts Label (Video) ...

  6. The anatomy of a laser label

    Science.gov (United States)

    Laser labeling of fruits and vegetables is an efficient alternative to adhesive tags. The advantages of this system are numerous. In general the label consists of alphanumerical characters formed by laser generated pinhole depressions that penetrate the produce’s surface creating visible markings. H...

  7. Do European consumers use nutrition labels?

    DEFF Research Database (Denmark)

    Wills, Josephine M.; Grunert, Klaus G.; Celemín, Laura Fernández;

    2009-01-01

    Nutrition labelling on food packages becomes more and more widespread in the European Union. Such information is not compulsory, unless a nutrition or health claim is made. However, how do consumers use nutrition information? Two European studies are currently assessing whether nutrition...... knowledge about nutrition and are able to use nutrition labels to identify healthier products within a category....

  8. 10 CFR 20.1904 - Labeling containers.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Labeling containers. 20.1904 Section 20.1904 Energy....1904 Labeling containers. (a) The licensee shall ensure that each container of licensed material bears... handling or using the containers, or working in the vicinity of the containers, to take precautions...

  9. 21 CFR 331.80 - Professional labeling.

    Science.gov (United States)

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Labeling § 331.80 Professional labeling... low phosphate diet to prevent formation of phosphate urinary stones, through the reduction...

  10. Synthesis of tritium-labeled fosfomycin

    Energy Technology Data Exchange (ETDEWEB)

    Mertel, H.E.; Meriwether, H.T. (Merck Sharp and Dohme Research Labs., Rahway, NJ (USA))

    1982-03-01

    Tritium gas was used as a labeling agent for the preparation of (1,2-/sup 3/H)fosfomycin. Introduction of tritium into a precursor, the synthesis including resolution of the intermediate racemic 1,2-epoxypropylphosphonic acid, and preparation of both amine and calcium salts of the labeled antibiotic are described.

  11. 9 CFR 101.4 - Labeling terminology.

    Science.gov (United States)

    2010-01-01

    ... Labeling terminology. Terms pertaining to identification and packaging of biological products shall mean: (a) Label. All written, graphic, or printed matter: (1) Upon or attached to a final container of a... other written, printed, or graphic matter accompanying the final container. (c) Final container....

  12. How to Read a Nutrition Facts Label

    Medline Plus

    Full Text Available ... Growth How to Read a Nutrition Facts Label (Video) KidsHealth > For Parents > How to Read a Nutrition Facts Label (Video) Print A A A Text Size en español Cómo leer las etiquetas de datos nutricionales (video) For Teens For Kids For Parents MORE ON ...

  13. STRATEGIC LABELING AND TRADE OF GMOS

    OpenAIRE

    Veyssiere, Luc; Giannakas, Konstantinos

    2004-01-01

    This paper systematically analyzes the strategic effects of national regulatory decisions on labeling of GM products and identifies the determinants of the non-cooperative Nash equilibrium labeling regimes in a small number of producing countries that compete for access in the world market for an agricultural product.

  14. 21 CFR 1271.370 - Labeling.

    Science.gov (United States)

    2010-04-01

    ...) You must label each HCT/P made available for distribution clearly and accurately. (b) The following information must appear on the HCT/P label: (1) Distinct identification code affixed to the HCT/P container, and assigned in accordance with § 1271.290(c); (2) Description of the type of HCT/P; (3)...

  15. Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

    Science.gov (United States)

    Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

    2016-03-01

    Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models.

  16. Traffic light labelling: traduzindo a rotulagem de alimentos Traffic light labeling: translating food labeling

    OpenAIRE

    Giovana Longo-Silva; Maysa Helena de Aguiar Toloni; José Augusto de Aguiar Carrazedo Taddei

    2010-01-01

    OBJETIVO: Apresentar uma adaptação do Traffic Light Labelling, ou "Semáforo Nutricional", adotado no Reino Unido e outros países da Europa, às normas vigentes no Brasil e classificar produtos industrializados comercializados no país. MÉTODOS: Esta ferramenta baseia-se na utilização das cores do semáforo para valorar concentrações de gorduras total, saturada e trans, açúcar, sódio e fibra correspondente a 100g ou 100mL do produto. O sinal vermelho indica que o nutriente está presente em quanti...

  17. Energy labeling for electric fans in Malaysia

    International Nuclear Information System (INIS)

    To reduce energy consumption in the residential sector, Malaysia Energy Commission is considering implementing energy labels for household electrical appliances including electric fans in 2005. The purpose of the energy labels is to provide the consumers a guideline to compare the size, features, price and efficiency of the appliance. This paper discusses the energy label for electric fans in this country based on Malaysian Standards developed by a technical committee that reviewed the performance of household electrical appliances. This study includes methodology for the calculation of the energy efficiency star rating and projected energy usage, performance requirements, details of the energy label and the requirements for the valid application in Malaysia. The label also can be adopted for other household electrical appliances with only slight modifications

  18. Tritium labelling of two new analgesic drugs

    International Nuclear Information System (INIS)

    The labelling with tritium of two arylpropionic esters was studied. The synthesis between 3H-Ibuprofen and the two unlabelled alcoholic moieties (Cl-Alkanol and CF3-Alkanol) was performed. Assuming that we got ready the acidic moiety, 3H-Ibuprofen, in our Laboratory, we attempted to label with tritium the alcoholic moiety and then go on to its esterification. Prior to labelling, thermic stability of 2-(4-(3-chlorophenyl)-1-piperazinyl) ethanol (Cl-Alkanol) was studied. As result of this study we had to change the labelling method, so that the Cl-Alkanol was unstable at 700C. Purification was accomplished through thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). Concentration, purity and specific activities of the two labelled compounds were determined by ultraviolet, HPLC and liquid scintillation techniques. (author)

  19. Recent developments in blood cell labeling research

    International Nuclear Information System (INIS)

    A number of recent developments in research on blood cell labeling techniques are presented. The discussion relates to three specific areas: (1) a new in vitro method for red blood cell labeling with /sup 99m/Tc; (2) a method for labeling leukocytes and platelets with /sup 99m/Tc; and (3) the use of monoclonal antibody technique for platelet labeling. The advantages and the pitfalls of these techniques are examined in the light of available mechanistic information. Problems that remain to be resolved are reviewed. An assessment is made of the progress as well as prospects in blood cell labeling methodology including that using the monoclonal antibody approach. 37 refs., 4 figs

  20. Simplified labeling process for medical image segmentation.

    Science.gov (United States)

    Gao, Mingchen; Huang, Junzhou; Huang, Xiaolei; Zhang, Shaoting; Metaxas, Dimitris N

    2012-01-01

    Image segmentation plays a crucial role in many medical imaging applications by automatically locating the regions of interest. Typically supervised learning based segmentation methods require a large set of accurately labeled training data. However, thel labeling process is tedious, time consuming and sometimes not necessary. We propose a robust logistic regression algorithm to handle label outliers such that doctors do not need to waste time on precisely labeling images for training set. To validate its effectiveness and efficiency, we conduct carefully designed experiments on cervigram image segmentation while there exist label outliers. Experimental results show that the proposed robust logistic regression algorithms achieve superior performance compared to previous methods, which validates the benefits of the proposed algorithms. PMID:23286072

  1. 49 CFR 172.416 - POISON GAS label.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false POISON GAS label. 172.416 Section 172.416... SECURITY PLANS Labeling § 172.416 POISON GAS label. (a) Except for size and color, the POISON GAS label... POISON GAS label and the symbol must be white. The background of the upper diamond must be black and...

  2. Near-optimal labeling schemes for nearest common ancestors

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Halvorsen, Esben Bistrup; Larsen, Kasper Green

    2013-01-01

    We consider NCA labeling schemes: given a rooted tree $T$, label the nodes of $T$ with binary strings such that, given the labels of any two nodes, one can determine, by looking only at the labels, the label of their nearest common ancestor. For trees with $n$ nodes we present upper and lower bou...

  3. Off-label uses of retinoids in dermatology

    Directory of Open Access Journals (Sweden)

    Wei Li

    2012-09-01

    Full Text Available Retinoids has been used widely in the topical and systemic treatments of various dermatoses: psoriasis, disorders of keratinization (DOK, keratotic genodermatosis, and severe acne. Moreover, it is also used in the treatment and/or chemoprevention of skin cancer and other neoplasms. Retinoids display key regulatory functions and most dermatologists are familiar with the FDA-approved indication of this medication. Retinoic acid is a potent signaling molecule that is essential for many biological processes, and its levels are tightly regulated by mechanisms that are only partially understood. This article will review these recent findings and attempt to synthesize their meaning to provide a view into the off-label uses of retinoids in dermatology with an emphasis on oral isotretinoin and acitrein.

  4. Plasmid DNA labelled with 14C or 3H

    International Nuclear Information System (INIS)

    Plasmid DNA labelled with 14C or 3H in thymine was isolated from the thymine-dependent strain of Escherichia coli 15 SPT bacteria. The specific activity of the plasmid DNA preparations lay in the range from 0.5 to 20 MBq/mg, their relative molecular weight was 1.7 x 106 dalton. Molecular weight, preparation purity, and the degree of damage of the plasmid DNA molecules were examined by UV absorption spectroscopy, by gel electrophoresis, and by electron micrography. The quality of the [thymine-2-14C] plasmid DNA was verified in a diagnostic test for the determination of the anti-dsDNA bonding activity in human serum. (author). 1 tab., 5 figs., 30 refs

  5. Molecule-by-Molecule Writing Using a Focused Electron Beam

    DEFF Research Database (Denmark)

    Van Dorp, Willem F.; Zhang, Xiaoyan; Feringa, Ben L.; Hansen, Thomas Willum; Wagner, Jakob Birkedal; De Hosson, Jeff Th. M.

    2012-01-01

    The resolution of lithography techniques needs to be extended beyond their current limits to continue the trend of miniaturization and enable new applications. But what is the ultimate spatial resolution? It is known that single atoms can be imaged with a highly focused electron beam. Can single...... atoms also be written with an electron beam? We verify this with focused electron-beam-induced deposition (FEBID), a direct-write technique that has the current record for the smallest feature written by (electron) optical lithography. We show that the deposition of an organometallic precursor on...... graphene can be followed molecule-by-molecule with FEBID. The results show that mechanisms that are inherent to the process inhibit a further increase in control over the process. Hence, our results present the resolution limit of (electron) optical lithography techniques. The writing of isolated...

  6. Gating capacitive field-effect sensors by the charge of nanoparticle/molecule hybrids.

    Science.gov (United States)

    Poghossian, Arshak; Bäcker, Matthias; Mayer, Dirk; Schöning, Michael J

    2015-01-21

    The semiconductor field-effect platform is a powerful tool for chemical and biological sensing with direct electrical readout. In this work, the field-effect capacitive electrolyte-insulator-semiconductor (EIS) structure - the simplest field-effect (bio-)chemical sensor - modified with citrate-capped gold nanoparticles (AuNPs) has been applied for a label-free electrostatic detection of charged molecules by their intrinsic molecular charge. The EIS sensor detects the charge changes in AuNP/molecule inorganic/organic hybrids induced by the molecular adsorption or binding events. The feasibility of the proposed detection scheme has been exemplarily demonstrated by realizing capacitive EIS sensors consisting of an Al-p-Si-SiO2-silane-AuNP structure for the label-free detection of positively charged cytochrome c and poly-d-lysine molecules as well as for monitoring the layer-by-layer formation of polyelectrolyte multilayers of poly(allylamine hydrochloride)/poly(sodium 4-styrene sulfonate), representing typical model examples of detecting small proteins and macromolecules and the consecutive adsorption of positively/negatively charged polyelectrolytes, respectively. For comparison, EIS sensors without AuNPs have been investigated, too. The adsorption of molecules on the surface of AuNPs has been verified via the X-ray photoelectron spectroscopy method. In addition, a theoretical model of the functioning of the capacitive field-effect EIS sensor functionalized with AuNP/charged-molecule hybrids has been discussed. PMID:25470772

  7. Drug transport mechanism of P-glycoprotein monitored by single molecule fluorescence resonance energy transfer

    Science.gov (United States)

    Ernst, S.; Verhalen, B.; Zarrabi, N.; Wilkens, S.; Börsch, M.

    2011-03-01

    In this work we monitor the catalytic mechanism of P-glycoprotein (Pgp) using single-molecule fluorescence resonance energy transfer (FRET). Pgp, a member of the ATP binding cassette family of transport proteins, is found in the plasma membrane of animal cells where it is involved in the ATP hydrolysis driven export of hydrophobic molecules. When expressed in the plasma membrane of cancer cells, the transport activity of Pgp can lead to the failure of chemotherapy by excluding the mostly hydrophobic drugs from the interior of the cell. Despite ongoing effort, the catalytic mechanism by which Pgp couples MgATP binding and hydrolysis to translocation of drug molecules across the lipid bilayer is poorly understood. Using site directed mutagenesis, we have introduced cysteine residues for fluorescence labeling into different regions of the nucleotide binding domains (NBDs) of Pgp. Double-labeled single Pgp molecules showed fluctuating FRET efficiencies during drug stimulated ATP hydrolysis suggesting that the NBDs undergo significant movements during catalysis. Duty cycle-optimized alternating laser excitation (DCO-ALEX) is applied to minimize FRET artifacts and to select the appropriate molecules. The data show that Pgp is a highly dynamic enzyme that appears to fluctuate between at least two major conformations during steady state turnover.

  8. Applying Semiconductor Technologies and Metrology Tools to Biomedical Research: Manipulation and Detection of Single Molecules

    Science.gov (United States)

    Berlin, Andrew A.; Sundararajan, Narayan; Koo, Tae-Woong

    2005-09-01

    Intel's Precision Biology research effort is working to combine Intel's expertise in nanotechnology with aspects of biology and medicine to create highly sensitive instrumentation for biomolecular analysis. The ability to manipulate, detect, and identify biological molecules at ultra-low concentrations is important for applications ranging from whole-genome DNA sequencing to protein-based early disease detection. In this paper we describe our work to develop a molecular labeling system based on Surface-Enhanced Raman Spectroscopy (SERS), to enable highly sensitive protein detection. We also present a set of microfluidic and spectroscopic techniques that our team has developed for transporting and identifying single molecules in solution.

  9. Biosynthesis of the D2 cell adhesion molecule: pulse-chase studies in cultured fetal rat neuronal cells

    DEFF Research Database (Denmark)

    Lyles, J M; Norrild, B; Bock, E

    1984-01-01

    chase times the Mr of both molecules increased to 187,000-201,000 (A) and 137,000-158,000 (B). These were similar to the sizes of D2-CAM labeled with [14C]glucosamine, [3H]fucose and [14C]mannosamine, indicating that the higher Mr species are glycoproteins. In the presence of tunicamycin, which...

  10. Resonance energy transfer in DNA duplexes labeled with localized dyes.

    Science.gov (United States)

    Cunningham, Paul D; Khachatrian, Ani; Buckhout-White, Susan; Deschamps, Jeffrey R; Goldman, Ellen R; Medintz, Igor L; Melinger, Joseph S

    2014-12-18

    The growing maturity of DNA-based architectures has raised considerable interest in applying them to create photoactive light harvesting and sensing devices. Toward optimizing efficiency in such structures, resonant energy transfer was systematically examined in a series of dye-labeled DNA duplexes where donor-acceptor separation was incrementally changed from 0 to 16 base pairs. Cyanine dyes were localized on the DNA using double phosphoramidite attachment chemistry. Steady state spectroscopy, single-pair fluorescence, time-resolved fluorescence, and ultrafast two-color pump-probe methods were utilized to examine the energy transfer processes. Energy transfer rates were found to be more sensitive to the distance between the Cy3 donor and Cy5 acceptor dye molecules than efficiency measurements. Picosecond energy transfer and near-unity efficiencies were observed for the closest separations. Comparison between our measurements and the predictions of Förster theory based on structural modeling of the dye-labeled DNA duplex suggest that the double phosphoramidite linkage leads to a distribution of intercalated and nonintercalated dye orientations. Deviations from the predictions of Förster theory point to a failure of the point dipole approximation for separations of less than 10 base pairs. Interactions between the dyes that alter their optical properties and violate the weak-coupling assumption of Förster theory were observed for separations of less than four base pairs, suggesting the removal of nucleobases causes DNA deformation and leads to enhanced dye-dye interaction. PMID:25397906

  11. Label-free surface plasmon sensing towards cancer diagnostics

    Science.gov (United States)

    Sankaranarayanan, Goutham

    The main objective of this thesis is to develop a conventional, home-built SPR bio-sensor to demonstrate bio-sensing applications. This emphasizes the understanding of basic concepts of Surface Plasmon Resonance and various interrogation techniques. Intensity Modulation was opted to perform the label-free SPR bio-sensing experiments due to its cost-efficient and compact setup. Later, label-free surface plasmon sensing was carried out to study and understand the bio-molecular interactions between (1). BSA and Anti BSA molecules and (2). Exosome/Liposome on thin metal (Au) films. Exosomes are cell-derived vesicles present in bodily fluids like blood, saliva, urine, epididymal fluid containing miRNAs, RNA, proteins, etc., at stable quantities during normal health conditions. The exosomes comprise varied constituents based on their cell origin from where they are secreted and is specific to that particular origin. However an exacerbated release is observed during tumor or cancer conditions. This increased level of exosomes present in the sample, can be detected using the SPR bio-sensor demonstrated in this thesis and effective thickness of adsorption on Au surface can be estimated. Also, chemically synthesized liposome particles were studied to determine if they can generate an equivalent sensor response to that of exosomes to consider them as an alternate. Finally a 10ppb Mercury (Hg) sensing was performed as part of Environment Monitoring application and results have been tabulated and compared.

  12. Nanoimprinted distributed feedback dye laser sensor for real-time imaging of small molecule diffusion

    DEFF Research Database (Denmark)

    Vannahme, Christoph; Dufva, Martin; Kristensen, Anders

    2014-01-01

    of different grating periods which result in distinct laser emission wavelengths. Imaging in two dimensions of space is enabled by focusing an image of the laser surface with a cylindrical lens onto the entrance slit of an imaging spectrometer. Imaging is demonstrated by monitoring of diffusing small......Label-free imaging is a promising tool for the study of biological processes such as cell adhesion and small molecule signaling processes. In order to image in two dimensions of space current solutions require motorized stages which results in low imaging frame rates. Here, a highly sensitive...... distributed feedback (DFB) dye laser sensor for real-time label-free imaging without any moving parts enabling a frame rate of 12 Hz is presented. The presence of molecules on the laser surface results in a wavelength shift which is used as sensor signal. The unique DFB laser structure comprises several areas...

  13. IRMS detection of testosterone manipulated with {sup 13}C labeled standards in human urine by removing the labeled {sup 13}C

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jingzhu, E-mail: wangjingzhu@chinada.cn [National Anti-Doping Laboratory, China Anti-Doping Agency, Beijing (China); Yang, Rui [Sport Science College, Beijing Sport University Beijing, Beijing (China); Yang, Wenning [School of Pharmacy, Beijing University of Chinese Medicine, Beijing (China); Liu, Xin; Xing, Yanyi; Xu, Youxuan [National Anti-Doping Laboratory, China Anti-Doping Agency, Beijing (China)

    2014-12-10

    Highlights: • {sup 13}C labeled testosterone can be used to adjust the isotope ratio of testosterone. • The novel testosterone cannot be detected by the regular IRMS method in doping test. • A method was explored to remove the labeled {sup 13}C. • The established method can be used to detect the manipulated testosterone. - Abstract: Isotope ratio mass spectrometry (IRMS) is applied to confirm testosterone (T) abuse by determining the carbon isotope ratios (δ{sup 13}C value). However, {sup 13}C labeled standards can be used to control the δ{sup 13}C value and produce manipulated T which cannot be detected by the current method. A method was explored to remove the {sup 13}C labeled atom at C-3 from the molecule of androsterone (Andro), the metabolite of T in urine, to produce the resultant (A-nor-5α-androstane-2,17-dione, ANAD). The difference in δ{sup 13}C values between Andro and ANAD (Δδ{sup 13}C{sub Andro–ANAD}, ‰) would change significantly in case manipulated T is abused. Twenty-one volunteers administered T manipulated with different {sup 13}C labeled standards. The collected urine samples were analyzed with the established method, and the maximum value of Δδ{sup 13}C{sub Andro–ANAD} post ingestion ranged from 3.0‰ to 8.8‰. Based on the population reference, the cut-off value of Δδ{sup 13}C{sub Andro–ANAD} for positive result was suggested as 1.2‰. The developed method could be used to detect T manipulated with 3-{sup 13}C labeled standards.

  14. Development of versatile isotopic labeling reagents for profiling the amine submetabolome by liquid chromatography–mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Ruokun; Huan, Tao; Li, Liang, E-mail: Liang.Li@ualberta.ca

    2015-06-30

    Highlights: • Two new reagents were developed for chemical isotope labeling mass spectrometry (MS). • They could be used to label amine-containing metabolites in a metabolomic sample. • The labeled metabolites could be detected with much improved sensitivity in MS. • One of the reagents could also help generate useful MS/MS spectra for structural analysis. • These reagents should be useful for quantitative metabolomics. - Abstract: Metabolomic profiling involves relative quantification of metabolites in comparative samples and identification of the significant metabolites that differentiate different groups (e.g., diseased vs. controls). Chemical isotope labeling (CIL) liquid chromatography–mass spectrometry (LC–MS) is an enabling technique that can provide improved metabolome coverage and metabolite quantification. However, chemical identification of labeled metabolites can still be a challenge. In this work, a new set of isotopic labeling reagents offering versatile properties to enhance both detection and identification are described. They were prepared by a glycine molecule (or its isotopic counterpart) and an aromatic acid with varying structures through a simple three-step synthesis route. In addition to relatively low costs of synthesizing the reagents, this reaction route allows adjusting reagent property in accordance with the desired application objective. To date, two isotopic reagents, 4-dimethylaminobenzoylamido acetic acid N-hydroxylsuccinimide ester (DBAA-NHS) and 4-methoxybenzoylamido acetic acid N-hydroxylsuccinimide ester (MBAA-NHS), for labeling the amine-containing metabolites (i.e., amine submetabolome) have been synthesized. The labeling conditions and the related LC–MS method have been optimized. We demonstrate that DBAA labeling can increase the metabolite detectability because of the presence of an electrospray ionization (ESI)-active dimethylaminobenzoyl group. On the other hand, MBAA labeled metabolites can be fragmented

  15. Development of versatile isotopic labeling reagents for profiling the amine submetabolome by liquid chromatography–mass spectrometry

    International Nuclear Information System (INIS)

    Highlights: • Two new reagents were developed for chemical isotope labeling mass spectrometry (MS). • They could be used to label amine-containing metabolites in a metabolomic sample. • The labeled metabolites could be detected with much improved sensitivity in MS. • One of the reagents could also help generate useful MS/MS spectra for structural analysis. • These reagents should be useful for quantitative metabolomics. - Abstract: Metabolomic profiling involves relative quantification of metabolites in comparative samples and identification of the significant metabolites that differentiate different groups (e.g., diseased vs. controls). Chemical isotope labeling (CIL) liquid chromatography–mass spectrometry (LC–MS) is an enabling technique that can provide improved metabolome coverage and metabolite quantification. However, chemical identification of labeled metabolites can still be a challenge. In this work, a new set of isotopic labeling reagents offering versatile properties to enhance both detection and identification are described. They were prepared by a glycine molecule (or its isotopic counterpart) and an aromatic acid with varying structures through a simple three-step synthesis route. In addition to relatively low costs of synthesizing the reagents, this reaction route allows adjusting reagent property in accordance with the desired application objective. To date, two isotopic reagents, 4-dimethylaminobenzoylamido acetic acid N-hydroxylsuccinimide ester (DBAA-NHS) and 4-methoxybenzoylamido acetic acid N-hydroxylsuccinimide ester (MBAA-NHS), for labeling the amine-containing metabolites (i.e., amine submetabolome) have been synthesized. The labeling conditions and the related LC–MS method have been optimized. We demonstrate that DBAA labeling can increase the metabolite detectability because of the presence of an electrospray ionization (ESI)-active dimethylaminobenzoyl group. On the other hand, MBAA labeled metabolites can be fragmented

  16. Labelling of endogenous target protein via N-S acyl transfer-mediated activation of N-sulfanylethylanilide.

    Science.gov (United States)

    Denda, Masaya; Morisaki, Takuya; Kohiki, Taiki; Yamamoto, Jun; Sato, Kohei; Sagawa, Ikuko; Inokuma, Tsubasa; Sato, Youichi; Yamauchi, Aiko; Shigenaga, Akira; Otaka, Akira

    2016-07-14

    The ligand-dependent incorporation of a reporter molecule (e.g., fluorescence dye or biotin) onto a endogenous target protein has emerged as an important strategy for elucidating protein function using various affinity-based labelling reagents consisting of reporter, ligand and reactive units. Conventional labelling reagents generally use a weakly activated reactive unit, which can result in the non-specific labelling of proteins in a ligand-independent manner. In this context, the activation of a labelling reagent through a targeted protein-ligand interaction could potentially overcome the problems associated with conventional affinity-based labelling reagents. We hypothesized that this type of protein-ligand-interaction-mediated activation could be accomplished using N-sulfanylethylanilide (SEAlide) as the reactive unit in the labelling reagent. Electrophilically unreactive amide-type SEAlide can be activated by its conversion to the corresponding active thioester in the presence of a phosphate salt, which can act as an acid-base catalyst. It has been suggested that protein surfaces consisting of hydrophilic residues such as amino, carboxyl and imidazole groups could function as acid-base catalysts. We therefore envisioned that a SEAlide-based labelling reagent (SEAL) bearing SEAlide as a reactive unit could be activated through the binding of the SEAL with a target protein. Several SEALs were readily prepared in this study using standard 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase protocols. These SEAL systems were subsequently applied to the ligand-dependent labelling of human carbonic anhydrase (hCA) and cyclooxyganese 1. Although we have not yet obtained any direct evidence for the target protein-mediated activation of the SEAlide unit, our results for the reaction of these SEALs with hCA1 or butylamine indirectly support our hypothesis. The SEALs reported in this study represent valuable new entries to the field of affinity-based labelling reagents

  17. A general method to improve fluorophores for live-cell and single-molecule microscopy.

    Science.gov (United States)

    Grimm, Jonathan B; English, Brian P; Chen, Jiji; Slaughter, Joel P; Zhang, Zhengjian; Revyakin, Andrey; Patel, Ronak; Macklin, John J; Normanno, Davide; Singer, Robert H; Lionnet, Timothée; Lavis, Luke D

    2015-03-01

    Specific labeling of biomolecules with bright fluorophores is the keystone of fluorescence microscopy. Genetically encoded self-labeling tag proteins can be coupled to synthetic dyes inside living cells, resulting in brighter reporters than fluorescent proteins. Intracellular labeling using these techniques requires cell-permeable fluorescent ligands, however, limiting utility to a small number of classic fluorophores. Here we describe a simple structural modification that improves the brightness and photostability of dyes while preserving spectral properties and cell permeability. Inspired by molecular modeling, we replaced the N,N-dimethylamino substituents in tetramethylrhodamine with four-membered azetidine rings. This addition of two carbon atoms doubles the quantum efficiency and improves the photon yield of the dye in applications ranging from in vitro single-molecule measurements to super-resolution imaging. The novel substitution is generalizable, yielding a palette of chemical dyes with improved quantum efficiencies that spans the UV and visible range. PMID:25599551

  18. Detecting single DNA molecule interactions with optical microcavities (Presentation Recording)

    Science.gov (United States)

    Vollmer, Frank

    2015-09-01

    Detecting molecules and their interactions lies at the heart of all biosensor devices, which have important applications in health, environmental monitoring and biomedicine. Achieving biosensing capability at the single molecule level is, moreover, a particularly important goal since single molecule biosensors would not only operate at the ultimate detection limit by resolving individual molecular interactions, but they could also monitor biomolecular properties which are otherwise obscured in ensemble measurements. For example, a single molecule biosensor could resolve the fleeting interaction kinetics between a molecule and its receptor, with immediate applications in clinical diagnostics. We have now developed a label-free biosensing platform that is capable of monitoring single DNA molecules and their interaction kinetics[1], hence achieving an unprecedented sensitivity in the optical domain, Figure 1. We resolve the specific contacts between complementary oligonucleotides, thereby detecting DNA strands with less than 2.4 kDa molecular weight. Furthermore we can discern strands with single nucleotide mismatches by monitoring their interaction kinetics. Our device utilizes small glass microspheres as optical transducers[1,2, 3], which are capable of increasing the number of interactions between a light beam and analyte molecules. A prism is used to couple the light beam into the microsphere. Ourr biosensing approach resolves the specific interaction kinetics between single DNA fragments. The optical transducer is assembled in a simple three-step protocol, and consists of a gold nanorod attached to a glass microsphere, where the surface of the nanorod is further modified with oligonucleotide receptors. The interaction kinetics of an oligonucleotide receptor with DNA fragments in the surrounding aqueous solution is monitored at the single molecule level[1]. The light remains confined inside the sphere where it is guided by total internal reflections along a

  19. On Labeled Traveling Salesman Problems

    DEFF Research Database (Denmark)

    Couetoux, Basile; Gourves, Laurent; Monnot, Jerome;

    2008-01-01

    We consider labeled Traveling Salesman Problems, defined upon a complete graph of n vertices with colored edges. The objective is to find a tour of maximum (or minimum) number of colors. We derive results regarding hardness of approximation, and analyze approximation algorithms for both versions of...... the problem. For the maximization version we give a -approximation algorithm and show that it is APX-hard. For the minimization version, we show that it is not approximable within n 1 − ε for every ε> 0. When every color appears in the graph at most r times and r is an increasing function of n the...... problem is not O(r 1 − ε )-approximable. For fixed constant r we analyze a polynomial-time (r + H r )/2-approximation algorithm (H r is the r-th harmonic number), and prove APX-hardness. Analysis of the studied algorithms is shown to be tight....

  20. ORGANIC FOOD LABELING AND CERTIFICATION

    Directory of Open Access Journals (Sweden)

    NICOLETA-ANDREEA NEACSU

    2011-04-01

    Full Text Available In the rush to produce more and more crops to satisfy growing demand producers have had to resort to using a lethal cocktail of pesticides to control disease and insect attack. This has lead to numerous international debates about unhealthy food, the effects of it and the measures that must be taken in order to avoid the harmful effects of genetically modified food consumption demonstrated by specialists. These debates evolve around the benefits of the organic products versus the pure trade trick outlined by some. The organic food movement has earned its well deserved place in many markets around the world. Its prestige is lately being widespread to vast parts of Eastern-Europe as well. Based on data collected from specialized reports and articles on organic products, the aim of this paper is to present the importance of organic products, the regulations on organic food and different labels used around the world in order to certify the organic food products.