A New SiF–Dipropargyl Glycerol Scaffold as a Versatile Prosthetic Group to Design Dimeric Radioligands: Synthesis of the [18F]BMPPSiF Tracer to Image Serotonin Receptors

A novel SiX–dipropargyl glycerol scaffold (X: H, F, or ¹⁸F) was developed as a versatile prosthetic group that provides technical advantages for the preparation of dimeric radioligands based on silicon fluoride acceptor pre‐ or post‐labeling with fluorine‐18. Rapid conjugation with the prosthetic group takes place in microwave‐assisted click conjugation under mild conditions. Thus, a bivalent homodimeric SiX–dipropargyl glycerol derivatized radioligand, [¹⁸F]BMPPSiF, with enhanced affinity was developed by using click conjugation. High uptake of the radioligand was demonstrated in 5‐HT_1A receptor‐rich regions in the brain with positron emission tomography. Molecular docking studies (rigid protein–flexible ligand) of BMPPSiF and known antagonists (WAY‐100635, MPPF, and MefWAY) with monomeric, dimeric, and multimeric 5‐HT_1A receptor models were performed, with the highest G score obtained for docked BMPPSiF: ?6.766 as compared with all three antagonists on the monomeric model. Multimeric induced‐fit docking was also performed to visualize the comparable mode of binding under in vivo conditions, and a notably improved G score of ?8.455 was observed for BMPPSiF. These data directly correlate the high binding potential of BMPPSiF with the bivalent binding mode obtained in the biological studies. The present study warrants wide application of the SiX–dipropargyl glycerol prosthetic group in the development of ligands for imaging with enhanced affinity markers for specific targeting based on peptides, nucleosides, and lipids.     

Humanization of 60.3, an anti-CD18 antibody; importance of the L2 loop

Monoclonal antibody 60.3 binds to the CD18 component of theß2 integrin family of adhesion molecules. 60.3 haspotential clinical application in blocking the neutrophilmediatedorgan damage which occurs following a myocardial infarct orhemorrhagic shock. Analysis of the nucleotide and deduced aminoacid sequences of murine 60.3 shows that the light chain containsno amino acid substitutions relative to the closest germlinesequence, while the heavy chain is heavily substituted. We reporthere the humanization of 60.3. The humanized antibody bindsto CD18-bearing cells with {small tilde}4-fold less affinitythan the murine or chimeric antibody. We have shown that modificationof amino acid L50 in the L2 loop of the humanized antibody resultsin loss of binding, while modification of a structural determinant(H71) for the H2 loop has no effect.     

强调材料——清华大学核能技术研究院花园的再设计

1设计意识核能研究院花园再设计的项目证明了朱育帆在本设计中的一个偏好的原发点:材料意识和对材料精确性的把握。从这种材料意识出发,他的设计赋予了这个地点一种新的愉悦氛围,甚至是对当代中国风景园林境遇的一种注释。     

Optical dilatometry for the control of microstructure development during sintering

An optical method for the in situ measurement of sintering shrinkage has been developed. It relies on a simple and robust CCD camera technique and is applicable up to high temperatures (2000 °C) and heating rates (10 K/min) in industrial furnace atmospheres. A resolution of less than 1 μm for a sample diameter of 10 mm has been achieved using a special geometrical arrangement and a smart image analysis algorithm. Systematic errors are small (<0.1%) and can be corrected by an additional measurement. A high reproducibility of shrinkage measurement has been observed in various sintering experiments. The optical dilatometer is very flexible: it has been used also for an accurate temperature calibration and for wetting experiments and it can be adjusted to different furnace types. Received: 17 May 2000 / Reviewed and accepted: 26 June 2000     

Investigations of the copper isotope effect in oxygen-deficient YBa2Cu3O7−δ

We present data on the copper isotope effect (⁶³Cu-⁶⁵Cu), C_u =-nT_c/nm_Cu, for two isotopic pairs of oxygen-deficient YBa₂Cu₃O_7–, where varies between 0.06 and 0.52. _Cu is below 0.01 at =0.06 (fully oxygenated), it takes values between –0.14 and –0.34 in the 60 K plateau. Larger negative values of _Cu are observed away from the plateau. The dependence of _Cu is similar to that of the pressure effect dnT_c/dP.     

Direct imaging of a two-dimensional silica glass on graphene

Large-area graphene substrates provide a promising lab bench for synthesizing, manipulating, and characterizing low-dimensional materials, opening the door to high-resolution analyses of novel structures, such as two-dimensional (2D) glasses, that cannot be exfoliated and may not occur naturally. Here, we report the accidental discovery of a 2D silica glass supported on graphene. The 2D nature of this material enables the first atomic resolution transmission electron microscopy of a glass, producing images that strikingly resemble Zachariasen's original 1932 cartoon models of 2D continuous random network glasses. Atomic-resolution electron spectroscopy identifies the glass as SiO(2) formed from a bilayer of (SiO(4))(2-) tetrahedra and without detectable covalent bonding to the graphene. From these images, we directly obtain ring statistics and pair distribution functions that span short-, medium-, and long-range order. Ab initio calculations indicate that van der Waals interactions with graphene energetically stabilizes the 2D structure with respect to bulk SiO(2). These results demonstrate a new class of 2D glasses that can be applied in layered graphene devices and studied at the atomic scale.     

From the mouse to the mass spectrometer: detection and differentiation of the endoproteinase activities of botulinum neurotoxins A-G by mass spectrometry

We have developed an assay (Endopep-MS) that detects the specific endoproteinase activities of all seven BoNT types by mass spectrometry (MS). Each BoNT type cleaves a unique site on proteins involved in neuronal transmission. Target peptide substrates based on these proteins identify a BoNT type by its enzymatic action on the substrate and the production of two peptide products, which are then detected by matrix-assisted laser desorption/ionization time-of-flight MS or liquid chromatography electrospray ionization MS/MS. We showed the ability to detect all seven toxin types in a multiplexed assay format. The detection limits achieved range from 0.039 to 0.625 mouse LD(50)/mL for toxin types A, B, E, and F in a buffer system. The Endopep-MS assay is the first to differentiate all seven BoNT types, is sensitive, specific, and has the potential to quantify toxin activity.     

Electronic passivation of silicon surfaces by halogens

We report the electronic passivation of a silicon surface by iodine termination. The resulting surface recombination velocity on Si(100) is less than 1 cm/s which is better than that obtained in concentrated hydrofluoric acid (HF). We have produced a surface recombination velocity of 20 cm/s using bromine. We present a simple model for these phenomena of a surface coverage of Si-X where X is a monovalently bonded halogen atom. The effectiveness of the passivation by halogens is shown to be limited by the oxidation of halogens by dissolved oxygen in solution. We demonstrate the use of halogen:methanol solutions as an alternative to HF for the control of silicon surface chemistry.     

Pharmacies during the transformation of health care. IV. Sociologic study of pharmacy service

In Slovakia, similarly as in the Czech Republic, marked changes in the pharmaceutical services have gradually been taking place since 1990. Principal legal and organizational changes have been connected also with the extent and standard of provided pharmaceutical services. The present paper reports the results of a questionnaire research regarding the evaluation of the standard of pharmaceutical services in the year 1995 where there existed both state-owned and private public pharmacies. The questionnaire research was carried out in 20 pharmacies of the Region of West Slovakia, 407 questionnaires were evaluated. The questionnaires were evaluated from the viewpoint of sociological classification of respondents (economically active persons, old-age pensioners) as well as the sex of pharmacy customers. The results confirmed relatively little significant differences between the satisfaction with pharmaceutical services either according to the sex or the social position of the respondents. A relatively significant proportion of the respondents have expressed critical views about the participation of the patient in covering the costs of drugs and slow execution of order of drugs.