bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin and its receptor: structure, function and evolution
Authors: De Meyts Pierre 
Published: November 2004

AbstractI present here a personal perspective on more than three decades of research into the structural biology of the insulin–receptor interaction. The solution of the three‐dimensional structure of insulin in 1969 provided a detailed understanding of the insulin surfaces involved in self‐assembly. In subsequent years, hundreds of insulin analogues were prepared by insulin chemists and molecular biologists, with the goal of relating the structure to the biological function of the molecule. The design of methods for direct receptor‐binding studies in the 1970s, and the cloning of the receptor in the mid 1980s, provided the required tools for detailed structure–function studies. In the absence of a full three‐dimensional structure of the insulin–receptor complex, I attempt to assemble the existing pieces of the puzzle generated by our and other laboratories, in order to generate a plausible mechanistic model of the insulin–receptor interaction that explains its kinetics and negative cooperativity. BioEssays 26:1351–1362, 2004. © 2004 Wiley Periodicals, Inc.
Synthesis, Structure, and Nonlinear Optical Properties of Cross‐Conjugated Perphenylated iso‐Polydiacetylenes
Authors: Zhao Yuming , Slepkov Aaron D. , Akoto Clement Osei , McDonald Robert , Hegmann Frank A. , Tykwinski Rik R. 
Published: November 2004

AbstractMonodisperse, cross‐conjugated perphenylated iso‐polydiacetylene (iso‐PDA) oligomers, ranging from monomer 15 to pentadecamer 25, have been synthesized by using a palladium‐catalyzed cross‐coupling protocol. Structural characteristics elucidated by X‐ray crystallographic analysis demonstrate a non‐planar backbone conformation for the oligomers due to the steric interactions between alkylidene phenyl groups. The electronic absorption spectra of the oligomers show a slight red‐shift of the maximum absorption wavelength as the chain length increases from dimer 17 b to pentadecamer 25, a trend that has saturated by the stage of nonamer 22. Fluorescence spectroscopy confirms that the pendent phenyl groups present on the oligomer framework enhance emission, and the relative emission intensity consistently increases as a function of chain length n. The molecular third‐order nonlinearities, γ, for this oligomer series have been measured via differential optical Kerr effect (DOKE) detection and show a superlinear increase as a function of the oligomer chain length n. Molecular modeling and spectroscopic studies suggest that iso‐PDA oligomers (n>7) adopt a coiled, helical conformation in solution.
Expeditious Asymmetric Synthesis of a Stereoheptad Corresponding to the C(19)–C(27)‐Ansa Chain of Rifamycins: Formal Total Synthesis of Rifamycin S
Authors: Turks Māris , Huang Xiaogen , Vogel Pierre 
Published: November 2004

AbstractIn the presence of sulfur dioxide and an acid promoter, (−)‐(1E,3Z)‐2‐methyl‐1‐((1S)‐1‐phenylethoxy)penta‐1,3‐dien‐3‐yl isobutyrate reacts with (Z)‐3‐(trimethylsilyloxy)pent‐2‐ene giving a silyl sulfinate intermediate that undergoes, in the presence of palladium catalyst, a desilylation and retro‐ene elimination of SO2 with formation of (−)‐(1Z,2S,3R,4S)‐1‐ethylidene‐2,4‐dimethyl‐5‐oxo‐3‐((1S)‐1‐phenylethoxy)‐heptyl isobutyrate as major product. This ethyl ketone undergoes cross‐aldol reaction with (2S)‐2‐methyl‐3‐[(tert‐butyldimethylsilyl)oxy]propanal giving an aldol that is reduced into a stereoheptad corresponding to the C(19)‐C(27)‐segment of Rifamycins with high diastereoselectivity and enantiomeric excess.
Growth, Structure, and Superconducting Properties of Bi2Sr2Ca2Cu3O10 and (Bi,Pb)2Sr2Ca2Cu3O10‐y Crystals.
Authors: Giannini E. , Garnier V. , Clayton N. , Musolino N. , Gladyshevskii R. , Fluekiger R. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Interaction of 5‐Aryl‐2,3‐dihydrofuran‐2,3‐diones with Functionally Substituted Hydrazides and Diaminoglyoxal Diphenylhydrazone.
Authors: Nekrasov D. D. , Kol'tsova S. V. , Radishevskaya M. A. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Polymerization of Cyclic Monomers. Part 11. Synthesis and Radical Polymerization of Various 2‐Cyclopropylacrylates.
Authors: de Meijere Armin , Bagutski Viktor , Zeuner Frank , Fischer Urs Karl , Rheinberger Volker , Moszner Norbert 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Stereoselective Synthesis of Bicyclo[4.2.1]nonane Skeletons by Ring‐Closing Metathesis: A New Versatile Methodology for the Efficient Assembly of Functionalized Cyclooctanoids.
Authors: Michaut Antoine , Miranda‐Garcia Sonia , Menendez J. Carlos , Rodriguez Jean 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis and Some Chemical Conversions of 2‐([2,2]‐5‐Paracyclophanyl)pyrrole.
Authors: Varlamov A. V. , Borisova T. N. , Nsabimana Boniface , Chernyshev A. I. , Aleksandrov G. G. , Voskressensky L. G. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis of 2‐Oxo‐2H‐chromene‐3‐carboxylic Acid (5‐Methyl‐3‐isoxazolyl) and (3‐Methyl‐5‐styryl‐4‐isoxazolyl) Amides as Potential Bioactive Compounds.
Authors: Rajanarendar E. , Ramu K. , Ramesh P. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Microwave‐Assisted Solvent‐Free Synthesis of a Quinoline‐3,4‐dicarboximide Library on Inorganic Solid Supports.
Authors: Mortoni Annalisa , Martinelli Marisa , Piarulli Umberto , Regalia Nickolas , Gagliardi Stefania 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis of 5‐Substituted Ethyl 3‐Oxo‐2H‐pyrazolo[4,3‐c]pyridine‐7‐carboxylates.
Authors: Bevk David , Jakse Renata , Golobic Amalija , Golic Ljubo , Meden Anton , Svete Jurij , Stanovnik Branko 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Novel Substituted 4‐Phenyl‐[1,3]dioxanes: Potent and Selective Orexin Receptor 2 (OX2R) Antagonists.
Authors: McAtee Laura C. , Sutton Steven W. , Rudolph Dale A. , Li Xiaobing , Aluisio Leah E. , Phuong Victor K. , Dvorak Curt A. , Lovenberg Timothy W. , Carruthers Nicholas I. , Jones Todd K. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Condensation of 4‐Hydroxy‐2‐thiazolines with 1,2‐Phenylenediamine as a Novel Effective Route to Thiazolo[3,4‐a]quinoxalines.
Authors: Mamedov Vakhid A. , Nurkhametova Ilsiyar Z. , Gubaidullin Aidar T. , Litvinov Igor A. , Tsuboi Sadao 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis and Biological Evaluation of Pteridine and Pyrazolopyrimidine Based Adenosine Kinase Inhibitors.
Authors: Gomtsyan Arthur , Didomenico Stanley , Lee Chih‐Hung , Stewart Andrew O. , Bhagwat Shripad S. , Kowaluk Elizabeth A. , Jarvis Michael F. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
The Preparation and Alkylation of a Butanedione‐Derived Chiral Glycine Equivalent and Its Use for the Synthesis of α‐Amino Acids and α,α‐Disubstituted Amino Acids.
Authors: Harding Christopher I. , Dixon Darren J. , Ley Steven V. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Condensation of Ethyl 2‐Oxoindoline‐3‐glyoxylate with o‐Aminophenol and o‐Phenylenediamine.
Authors: Bolotov V. V. , Kovalenko S. N. , Kovaleva S. V. , Stepanenko V. I. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
(E)‐Cycloalkenes and (E,E)‐Cycloalkadienes by Ring Closing Diyne‐ or Enye‐yne Metathesis/Semi‐reduction.
Authors: Lacombe Fabrice , Radkowski Karin , Seidel Guenter , Fuerstner Alois 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Microwave‐Assisted, Tin‐Mediated, Regioselective 3‐O‐Alkylation of Galactosides.
Authors: Ballell Lluis , Joosten John A. F. , el Maate Fatna Ait , Liskamp Rob M. J. , Pieters Roland J. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
A Library Synthesis of 4‐Hydroxy‐3‐methyl‐6‐phenylbenzofuran‐2‐carboxylic Acid Ethyl Ester Derivatives as Antitumor Agents.
Authors: Hayakawa Ichiro , Shioya Rieko , Agatsuma Toshinori , Furukawa Hidehiko , Naruto Shunji , Sugano Yuichi 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Metal Complexes with Novel Ambidentate Ligands: β‐Enaminovinylketones with Annelated 1,2‐Benzothiazine‐1,1‐Dioxide Fragment and Antipyrine Substituent
Authors: Garnovskii A. D. , Anpilova E. L. , Antsyshkina A. S. , Bicherov A. V. , Korshunov O. Yu. , Vasil'chenko I. S. , Uraev A. I. , Kharisov B. I. , Blanko L. M. , Sadikov G. G. , et al. et al. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Fine Tuning of MLCT States in New Mononuclear Complexes of Ruthenium(II) Containing Tris(1‐pyrazolyl)methane, 2,2′‐Bipyridine and Aromatic Nitrogen Heterocycles
Authors: Katz Néstor E. , Romero Isabel , Llobet Antoni , Parella Teodor , Benet‐Buchholz Jordi 
Published: November 2004

AbstractThe syntheses of new mononuclear ruthenium(II) complexes of the type: [Ru(bpy)(L)(tpm)](PF6)2 {tpm = tris(1‐pyrazolyl)methane; bpy = 2,2′‐bipyridine; L = pz (pyrazine; 1), 4,4′‐bpy (4,4′‐bipyridine; 2), and bpe [trans‐1,2‐bis(4‐pyridyl)ethylene; 3]} are described, together with their spectroscopic, electrochemical, and photophysical properties. A complete assignment of the NMR resonances of the three species could be made in CD3CN by bidimensional techniques. A fine tuning of the energies of MLCT (metal‐to‐ligand charge transfer) states in these complexes is disclosed when comparing, in CH3CN, the values of their maximum absorption wavelengths for the most intense visible bands (λmax) and their redox potentials for the RuIII/RuII couples; this effect, relevant to the design of efficient photocatalysts, can be attributed to a decreasing order of dπ(Ru) → π*(2,2′‐bpy) backbonding when decreasing the distance between both N atoms in the aromatic nitrogen heterocycle L that acts in a monodentate manner. Only the species with L = bpe emits at room temperature, pointing to the conclusion that MLCT excited states in this series become higher in energy than dd excited states when the value of λmax is lower than 400 nm. These species are also useful building blocks for new dinuclear mixed‐valent complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Acrylamide in heated potato products – analytics and formation routes
Authors: Weisshaar Rüdiger 
Published: November 2004

AbstractAcrylamide is a highly polar, water‐soluble molecule with low, but significant volatility. Most common methods for determination of acrylamide are high performance liquid chromatography‐tandem mass spectrometry (LC‐MS‐MS), gas chromatography‐mass spectrometry (GC‐MS) after bromination, GC‐MS without and LC‐MS after derivatisation with mercaptobenzoic acid. The different clean‐up procedures used are presented and the advantages and disadvantages of the individual methods are discussed. Acrylamide is formed during food preparation if free asparagine and reducing sugars are present, water activity is low and the product temperature exceeds 100 °C. The influence of different parameters on acrylamide formation in model systems is discussed. In fried potatoes the greatest amount of acrylamide is formed from asparagine and reducing sugars. Alternative routes of formation, as for example via acrolein and acrylic acid are much less important.
Chemistry, formation and occurrence of genotoxic heterocyclic aromatic amines in fried products
Authors: Murkovic Michael 
Published: November 2004

AbstractHeterocyclic amines (HAs) are formed during heating of meat or fish. The precursors necessary for formation of these heterocyclic amines are amino acids that react with carbohydrates and creatinine. Creatinine is needed for the formation of polar amines with an imidazo‐quinoline or an imidazo‐quinoxaline structure. For the formation of the non‐polar amines no creatinine is needed. At temperatures of above 150 °C these substances are formed in the low ppb range. However, when the temperature is increased or the heating time is prolonged the concentration of the amines can reach levels of above 100 ppb. Heterocyclic amines are mutagenic in bacterial and animal test systems and carcinogenic in rodents. As the heterocyclic amines are not mutagenic by themselves they have to be activated with cytochrome P450 enzymes and N‐acetyl‐transferases or sulfotransferases. Epidemiological studies have revealed that the cancer risk is strongly associated with the uptake of thoroughly roasted meat in which the heterocyclic amines occur. As these substances are formed inherently, measures have to be taken to reduce the formation in meat or fish during cooking. These measures range from changing cooking habits to use with additives or breeding of animals with a genetically determined lower HA forming capability of the meat.
hOGG1 Ser326Cys polymorphism and G:C‐to‐T:A mutations: No evidence for a role in tobacco‐related non small cell lung cancer
Authors: Hu Ying Chuan , Ahrendt Steven A. 
Published: November 2004

AbstractHuman 8‐oxoguanine DNA glycosylase 1 (hOGG1) plays a major role in the repair of 8‐hydroxyguanine, one of the major forms of DNA damage generated by reactive oxygen species in tobacco smoke. If left unrepaired by hOGG1, 8‐hydroxyguanine can produce G:C‐to‐T:A transversions. Recent studies have suggested that the hOGG1 Ser326Cys polymorphism is associated with both a decrease in enzyme activity and an increased risk of lung cancer. To define the interaction between tobacco carcinogens, hOGG1‐mediated DNA repair and DNA damage, we examined the role of the hOGG1 Ser326Cys polymorphism in mutation of the p53 gene in non small cell lung cancer (NSCLC). Tumor and nonneoplastic DNA were collected from 141 cigarette smokers with NSCLC. p53 mutations were detected by direct dideoxy sequencing and/or the GeneChip p53 assay in 74 of the 141 (52%) tumors. hOGG1 codon 326 polymorphisms were identified by polymerase chain reaction‐restriction fragment length polymorphism analysis. The distribution of hOGG1 codon 326 genotypes was Ser/Ser, 90 of 141 (64%); Ser/Cys, 45 of 141 (32%); and Cys/Cys, 6 of 141 (4%). p53 mutations were significantly (p = 0.04) less common in NSCLC from patients with codon 326 Ser/Cys or Cys/Cys genotypes (21 of 51; 41%) than in NSCLC from Ser/Ser homozygotes (53 of 90; 59%). The decrease in p53 mutation frequency among carriers of the Cys allele was more evident in lung squamous cell cancer [7 of 17 (41%) for Cys/Cys and Ser/Cys vs. 27 of 38 (71%) for Ser/Ser; p = 0.04] than in nonbronchoalveolar adenocarcinoma [11 of 26 (42%) for Cys/Cys and Ser/Cys vs. 20 of 35 (57%) for Ser/Ser; p = 0.25]. The prevalence of G:C‐to‐T:A transversions was similar among hOGG1 codon 326 genotypes. In summary, the hOGG1 codon 326 Cys allele was associated with a decrease in p53 mutations and no effect on G:C‐to‐T:A transversions in NSCLC. This decrease in p53 mutations in vivo is not consistent with a decrease in the repair of 8‐hydroxyguanine among carriers of the hOGG1 codon 326 Cys allele in vitro. © 2004 Wiley‐Liss, Inc.
Charge derivatization by 4‐sulfophenyl isothiocyanate enhances peptide sequencing by post‐source decay matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry
Authors: Marekov Lyuben N. , Steinert Peter M. 
Published: November 2004

AbstractHigh‐sensitivity, rapid identification of proteins in proteomic studies normally uses a combination of one‐ or two‐dimensional electrophoresis together with mass spectrometry. The simplicity and sensitivity of matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) have increased its application in recent years. The most common method of ‘peptide fingerprinting’ often may not provide robust identification. Normally additional sequence information by post‐source decay (PSD) MALDI‐TOFMS provides additional constraints for database searches to achieve highly confident results. Here we describe a derivatization procedure to facilitate the acquisition of such sequence information. Peptide digests from a skin‐expressed protein were modified with 4‐sulfophenyl isothiocyanate. The resulting peptides carry a fixed negative charge at the N‐terminal end and the resulting PSD spectrum is dominated by C‐terminal y‐type ions. The sequence information in most cases can be obtained manually or with simple programming tools. Methods of optimizing the procedure and increasing the sensitivity are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Multiple lithium exchange under lithium cationization of cyclodextrins
Authors: Madhusudanan K. P. 
Published: November 2004

AbstractMultiple lithium exchange is observed during electrospray ionization of α‐, β‐ and γ‐cyclodextrins from aqueous methanolic solution containing LiOH. Apart from [M + Li]+ and [M + nLi − (n − 1)H]+ ions, abundant multiply lithiated doubly charged ions corresponding to [M + nLi − (n − 2)H]2+ ions were observed. At least six lithium exchanges in α‐cyclodextrin, seven in β‐cyclodextrin and eight in γ‐cyclodextrin were noted. The propensity of multiply lithiated doubly charged ions is much less in the open‐ended maltoheptaose. It appears that during droplet or cluster formation and subsequent desolvation, LiOH trapped in the cavity of cyclodextrin reacts to form multiply lithiated ions. The singly charged [M + Li]+ and doubly charged [M + 2Li]2+ ions fragment by glycosidic cleavages, giving B series of ions, whereas the multiply lithiated ions fragment by cross ring cleavages (2, 4A or O, 2X) followed by glycosidic cleavage. From the tandem mass spectra, it appears that a maximum of two lithium exchanges occur in one sugar unit in these cyclodextrins. Copyright © 2003 John Wiley & Sons, Ltd.
Structural distinction among inositol phosphate isomers using high‐energy and low‐energy collisional‐activated dissociation tandem mass spectrometry with electrospray ionization
Authors: Hsu Fong‐Fu , Turk John , Gross Michael L. 
Published: November 2004

AbstractElectrospray (ESI) collisional‐activated dissociation (CAD) tandem mass spectrometric methods for the structural characterization of inositol phosphates (InsPs) using both quadrupole and sector mass spectrometers are described. Under low‐energy CAD, the [M + H]+ ions of the positional isomers of inositol phosphates, including inositol mono‐, bis‐ and trisphosphates, yield distinguishable product‐ion spectra, which are readily applicable for isomer differentiation. In contrast, the product‐ion spectra arising from high‐energy CAD (2 keV collision energy, floating at 50%) tandem sector mass spectrometry are less applicable for isomer identification. The differences in the product‐ion spectrum profiles among the aforementioned InsP isomers become more substantial and differentiation of positional isomers can be achieved when the collison energy is reduced to 1 keV (floating at 75%). These results demonstrate that the applied collision energies play a pivotal role in the fragmentations upon CAD. The product‐ion spectra are similar among the positional isomers of inositol tetrakisphosphates and of inositol pentakisphosphates. Thus, isomeric distinction for these two inositol polyphosphate classes could not be established by the tandem mass spectrometric methods that have achieved such distinctions for the less highly phosphorylated inositol phosphate classes. Under both high‐ and low‐energy CAD, the protonated molecular species of all InsPs undergo similar fragmentation pathways, which are dominated by the consecutive losses of H2O, HPO3 and H3PO4. Copyright © 2003 John Wiley & Sons, Ltd.
C1‐Symmetric Heterocyclic Zirconocenes as Catalysts for Propylene Polymerization, 1
Authors: Nifant'ev Ilya E. , Laishevtsev Ilya , Ivchenko Pavel V. , Kashulin Igor A. , Guidotti Simona , Piemontesi Fabrizio , Camurati Isabella , Resconi Luigi , Klusener Peter A. A. , Rijsemus Jos J. H. , de Kloe Kees P. , Korndorffer Frans M. 
Published: November 2004

AbstractSummary: The synthesis of C1‐symmetric zirconocene complexes bearing the 2,5‐dimethyl‐7H‐cyclopenta[1,2‐b:4,3‐b′]dithiophene ligand (S2‐3) linked to substituted cyclopentadienes is described. Different syntheses of S2‐3, the common intermediate for the preparation of these complexes, are discussed. Many of these complexes have been found to be highly active in propylene polymerization, to require very low amounts of methylalumoxane to be activated, and to produce poly(propylene)s of low isotacticity and melting points. 13C NMR analysis shows that the poly(propylene)s are fully regioregular and that the stereoerrors are randomly distributed, as shown by the enantiomorphic‐site triad test E ≈ 1. The experimental pentad distribution was fitted using a two‐site model with different probability parameters for each site. The probability of chain back‐skip was also taken into account. The molecular weight and crystallinity of the poly(propylene)s are dependent upon the type of substituents on the cyclopentadienyl ring, and the correlation between mmmm content and melting point of the PP confirms the random distribution of stereoerrors.Correlation between % mmmm pentad and melting point.magnified imageCorrelation between % mmmm pentad and melting point.
Discriminating Influence of α‐ and Methylated β‐Cyclodextrins on Complexation and Polymerization of Diacrylate and Dimethacrylate Monomers
Authors: Sarvothaman Mahesh Kumar , Ritter Helmut 
Published: November 2004

AbstractSummary: Host‐guest complexes of α‐cyclodextrin (α‐CD) and methylated β‐cyclodextrin (Me‐β‐CD) with diacrylates and dimethacrylates of butan‐1,4‐diol and hexan‐1,6‐diol at varying stoichiometries were studied. The complexes were analyzed by means of 1H NMR, two‐dimensional ROESY spectroscopy and Job's curves, which clearly revealed the discriminating influence of the two hosts towards complex formation. The corresponding polymers were obtained using a redox initiator system in water. Thermal analysis and IR measurements of the polymers provided evidence for the existence of a polyrotaxane architecture.Proposed structure of the cross‐linked polymers obtained by the redox polymerization of the Me‐β‐CD complexed monomers.imageProposed structure of the cross‐linked polymers obtained by the redox polymerization of the Me‐β‐CD complexed monomers.
Linear Viscoelastic Behavior of Unentangled Polymer Melts via Non‐Equilibrium Molecular Dynamics
Authors: Cifre José Gines Hernández , Hess Siegfried , Kröger Martin 
Published: November 2004

AbstractSummary: We present and assess the use of non‐equilibrium molecular dynamics (NEMD) simulation method for the direct study of the linear viscoelastic behavior of polymer melts. The polymer melt is modeled by a collection of repulsive, anharmonic multibead chains subjected to small amplitude oscillatory shear flow. We present results for chain lengths below the critical entanglement length and obtain good agreement with theoretical results for the viscoelastic behavior of melts of low molecular weight. The range of oscillation frequencies attainable in the simulation is of a few decades. Thus we use, as in experiments, a time‐temperature superposition rule to extend the frequency domain. As a side result, we confirm the so‐called Cox‐Merz rule.Snapshot from a non‐equilibrium molecular dynamics (3D) simulation of a polymer melt with 100 chains and 40 beads.magnified imageSnapshot from a non‐equilibrium molecular dynamics (3D) simulation of a polymer melt with 100 chains and 40 beads.