On functions having Cauchy differences in some prescribed sets

Summary AssumeE is a real topological vector space,F is a real Banach space,K is a discrete subgroup ofF andC is a symmetric, convex and compact subset ofF such thatK (6C) = {0}. If a functionh:E F is continuous at at least one point andh(x + y) – h(x) – h(y) K + C for allx, y E, then there exists a continuous linear functiona:E F such thath(x) – a(x) K + C for everyx E.     

Selective modification of the 2-position of pyridoxol

Pyridoxol, protected by acetylation of the hydroxyl groups, has been converted to its N-oxide which upon reaction with perfluoroacetie anhydride yields a 2-nor-2-hydroxymethylpyridoxol derivative as an intermediate. This compound undergoes acyl migration from the 3-position. Protection of the pyridoxol hydroxyls by benzylalion followed by the same treatment yields the unrearranged α²-hydroxy derivative. This compound has been converted to a series of α²-substituted pyridoxols (X = -Cl, -Br, -OCOCH₃, -OCH₃, -OC₂H₅).     

Luminescence spectroscopy of matrix-isolated z 6P state atomic manganese

The relaxation of electronically excited atomic manganese isolated in solid rare gas matrices is observed from recorded emission spectra, to be strongly site specific. z 6P state excitation of Mn atoms isolated in the red absorption site in Ar and Kr produces narrow a 4D and a 6D state emissions while blue-site excitation produces z 6P state fluorescence and broadened a 4D and a 6D emissions. MnXe exhibits only a single thermally stable site whose emission at 620 nm is similar to the broad a 6D bands produced with blue-site excitation in Ar and Kr. Thus in Ar(Kr), excitation of the red site at 393 (400) nm produces narrow line emissions at 427.5 (427.8) and 590 (585.7) nm. From their spectral positions, linewidths, and long decay times, these emission bands are assigned to the a 4D72 and a 6D92 states, respectively. Excitation of the blue site at 380 (385.5) nm produces broad emission at 413 (416) nm which, because of its nanosecond radiative lifetime, is assigned to resonance z 6P --> a 6S fluorescence. Emission bands at 438 (440) and 625 (626.8) nm, also produced with blue-site excitation, are broader than their red-site equivalents at 427.5 and 590 nm (427.8 and 585.7 nm in Kr) but from their millisecond and microsecond decay times are assigned to the a 4D and a 6D states. The line features observed in high resolution scans of the red-site emission at 427.5 and 427.8 nm in MnAr and MnKr, respectively, have been analyzed with the W(p) optical line shape function and identified as resolved phonon structure originating from very weak (S=0.4) electron-phonon coupling. The presence of considerable hot-phonon emission (even in 12 K spectra) and the existence of crystal field splittings of 35 and 45 cm(-1) on the excited a 4D72 level in Ar and Kr matrices have been identified in W(p) line shape fits. The measured matrix lifetimes for the narrow red-site a 6D state emissions (0.29 and 0.65 ms) in Ar and Kr are much shorter than the calculated (3 s) gas phase value. With the lifetime of the metastable a 6D92 state shortened by four orders of magnitude in the solid rare gases, it is clear that the probability of the "forbidden" a 6D --> a 6S atomic transition is greatly enhanced in the solid state. A novel feature identified in the present work is the large width and shifted 4D and 6D emissions produced for Mn atoms isolated in the blue sites of Ar and Kr. In contrast, these states produce narrow, unshifted (gas-phase-like) 4D and 6D state emissions from the red site.     

Determination of 8-hydroxy-2'-deoxyguanosine in untreated urine by capillary electrophoresis with UV detection

A capillary electrophoresis method with UV detection was developed for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in untreated urine samples. The calibration graph for 8-OHdG in urine is linear in the concentration range 10-500 mg/l. and the detection limit is 5 mg/l (17 microM). 8-OHdG was determined in urine from oncological patients treated by radiation therapy. Its concentrations relative to creatinine were found to be in the range 10-47 microg 8-OHdG/l mg creatinine (4-19 micromol 8-OHdG/mmol creatinine). The overall time of the analysis of a urine sample was less than 15 min.     

Preparations and spectroscopic studies of organotin complexes of diclofenac

The reactions of the potent and widely used anti-inflammatory drug diclofenac, HL, with diorganotin(IV) oxides were studied. The dimeric tetraorganodistannoxane complexes [Me(2)LSnOSnLMe(2)](2), [Bu(2)LSnOSnLBu(2)](2), [Ph(2)LSnOSnLPh(2)](2) and the dibutyltin complex [Bu(2)SnL(2)], have been prepared and structurally characterized in the solid state by means of vibrational and 119Sn M?ssbauer spectroscopy. Determination of lattice dynamics by temperature-dependent 119Sn M?ssbauer spectroscopy. From the variable-temperature M?ssbauer effect, the Debye temperature was determined. The complexes have been characterized in solution by NMR (1H and 13C) spectroscopy. Vibrational, M?ssbauer, and NMR data are discussed in terms of the proposed structures.     

Simultaneous quantification of terpenelactones and flavonol aglycones in hydrolyzed ginkgo biloba extract by liquid chromatography with inline ultraviolet and evaporative light scattering detection

We report here a liquid chromatography (LC) method with inline ultraviolet/evaporative light scattering (UV/ELS) detection for the simultaneous quantification of the terpenelactones and flavonol aglycones in a single sample of hydrolyzed Ginkgo biloba extract (GBE). The sample is hydrolyzed by a rapid and convenient oven heating method for 1 h at 90 degrees C with 10% hydrochloric acid. The 1 h hydrolysis was found to be equivalent to the 2.25 h reflux treatment for dry powder extract, where total flavonol glycosides were 28.4 and 28.1%, respectively. Acceptable precision was achieved for total terpenelactones [relative standard deviation (RSD) = 4.8%] by ELS detection, and total flavonol aglycones (RSD = 2.3%) by UV detection. The analytical range was 1.5 to 7.3% (w/w) for the individual terpenelactones (ELS) and 2.5 to 15.0% (w/w) for the individual glycosides (UV) calculated from the aglycones quercetin, kaempferol, and isorhamnetin. This improved method allows for the first time high throughput sample preparation coupled with the quantification of the predominant compounds generally used for quality control of GBE in a single assay.     

Design of a calcium-binding protein with desired structure in a cell adhesion molecule

Ca2+, "a signal of life and death", controls numerous cellular processes through interactions with proteins. An effective approach to understanding the role of Ca2+ is the design of a Ca2+-binding protein with predicted structural and functional properties. To design de novo Ca2+-binding sites in proteins is challenging due to the high coordination numbers and the incorporation of charged ligand residues, in addition to Ca2+-induced conformational change. Here, we demonstrate the successful design of a Ca2+-binding site in the non-Ca2+-binding cell adhesion protein CD2. This designed protein, Ca.CD2, exhibits selectivity for Ca2+ versus other di- and monovalent cations. In addition, La3+ (Kd 5.0 microM) and Tb3+ (Kd 6.6 microM) bind to the designed protein somewhat more tightly than does Ca2+ (Kd 1.4 mM). More interestingly, Ca.CD2 retains the native ability to associate with the natural target molecule. The solution structure reveals that Ca.CD2 binds Ca2+ at the intended site with the designed arrangement, which validates our general strategy for designing de novo Ca2+-binding proteins. The structural information also provides a close view of structural determinants that are necessary for a functional protein to accommodate the metal-binding site. This first success in designing Ca2+-binding proteins with desired structural and functional properties opens a new avenue in unveiling key determinants to Ca2+ binding, the mechanism of Ca2+ signaling, and Ca2+-dependent cell adhesion, while avoiding the complexities of the global conformational changes and cooperativity in natural Ca2+-binding proteins. It also represents a major achievement toward designing functional proteins controlled by Ca2+ binding.     

Live biotherapeutic products: the importance of a defined regulatory framework

Probiotics have been defined as “Live microorganisms that when administered in adequate amounts confer a health benefit on the host”. This definition covers a wide range of applications, target populations and (combinations of) microorganisms. Improved knowledge on the importance of the microbiota in terms of health and disease has further diversified the potential scope of a probiotic intervention, whether intended to reach the market as a food, a food supplement or a drug, depending on the intended use. However, the increased interest in the clinical application of probiotics may require specific attention given their administration in a diseased population. In addition to safety, the impact of the type of product, in terms of quality, production method and, e.g., the acceptance of side effects, is now part of the current regulatory constraints for developers. In the European Union, foods are regulated by the European Food Safety Authority and drugs by the European Medicines Agency; in the United States, the Food and Drug Administration (FDA) deals with both categories. More recently, the FDA has defined a new “live biotherapeutic products” (LBP) category, clarifying pharmaceutical expectations. Since 2019, the quality requirements for this category of drug products have also been clarified by the European Pharmacopoeia (Ph. Eur.). Similar to all products intended to prevent or treat diseases, LBPs will have to be registered as medicinal products to reach the market in the US and in Europe. In this area, regulatory authorities and the pharmaceutical industry will routinely use guidelines of the “International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use” (ICH). Although ICH guidelines are not legally binding, they provide very important recommendations, recognized by almost all drug authorities in the world. In this review, we discuss some aspects of this regulatory framework, especially focusing on products with an intended use in a diseased or vulnerable target population.Subject terms: Biological therapy, Biologics     

New nickel(II), copper(II), platinum(II) and palladium(II) complexes of a multidentate sulfur–nitrogen chelating agent

A new, potentially polydentate sulfur–nitrogen chelating agent, 2,6–bis(N-methyl-S-methyldithiocarbazato)pyridine (L) has been synthesized and characterized. With nickel(II) salts, the ligand yields complexes of empirical formula NiLX2·nH2O (X=Cl−, NCS− or NO3−; n=0 or 1) in which it behaves as a quadridentate NSSN chelating agent, coordinating to the nickel(II) ion via the two amino nitrogen atoms and the two sulfur atoms. Magnetic and spectral evidence support a distorted octahedral structure for these complexes. The ligand reacts with copper(II), platinum(II) and palladium(II) salts to yield homo-binuclear complexes of general formula [M2LX4]·nSol (M=CuII, PtII or PdII; X=Cl− or Br−; n=0.5, 1 or 2; Sol=H2O, MeOH or MeCOMe), in which each of the metal ions is in a square-planar environment. These complexes have been characterized by a variety of physicochemical techniques. This revised version was published online in June 2006 with corrections to the Cover Date.     

1H-pyrazolo[3,4-d]thieno[2,3-b]pyridine and its derivatives

The synthesis of the parent ring system and some of the derivatives of 1H-pyrazolo[3,4-d]thieno[2,3-b]pyridine are described.