bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional disomy of Xp including duplication of DAX1 gene with sex reversal due to t(X;Y)(p21.2;p11.3)
Authors: Sanlaville Damien , Vialard François , Thépot François , Vue‐Droy Luce , Ardalan Azarnouche , Nizard Patrice , Corré Alain , Devauchelle Bernard , Martin‐Denavit Tanguy , Nouchy Marc , Malan Valérie , Taillemite Jean‐Louis , Portnoï Marie‐France 
Published: May 2004

AbstractTranslocations involving the short arms of the X and Y in human chromosomes are uncommon. One of the best‐known consequences of such exchanges is sex reversal in 46,XX males and some 46,XY females, due to exchange in the paternal germline of terminal portions of Xp and Yp, including the SRY gene. Translocations of Xp segments to the Y chromosome result in functional disomy of the X chromosome with an abnormal phenotype and sex reversal if the DSS locus, mapped in Xp21, is present. We describe a 7‐month‐old girl with severe psychomotor retardation, minor anomalies, malformations, and female external genitalia. Cytogenetic analysis showed a 46,X,mar karyotype. The marker was identified as a der(Y)t(Xp;Yp) by fluorescence in situ hybridisation analysis. Further studies with specific locus probes of X and Y chromosomes made it possible to clarify the break points and demonstrated the presence of two copies of the DAX1 gene, one on the normal X chromosome and one on the der(Y). The karyotype of the child was: 46,X,der(Y)t(X;Y)(p21.2;p11.3). The syndrome resulted from functional disomy Xp21.2‐pter, with sex reversal related to the presence of two active copies of the DAX1 gene located in Xp21. Few cases of Xp disomy with sex reversal have been reported, primarily related to Xp duplications with 46,XY karyotype, and less often to Xp;Yq translocations. To our knowledge, our patient with sex reversal and a t(Xp;Yp) is the second reported case. © 2004 Wiley‐Liss, Inc.
Research and developments of a multi‐modal MIR engine for commercial applications in East Asia1
Authors: Jang Jyh‐Shing Roger , Lee Hong‐Ru , Chen Jiang‐Chuen , Lin Cheng‐Yuan 
Published: May 2004

AbstractThis article describes the research and development of an efficient Music Information Retrieval (MIR) engine that is embedded in a karaoke software package targeted for Asian people's need of music retrieval. The MIR engine has a multi‐modal interface that allows queries by singing, humming, tapping, speaking, and writing. In particular, we discuss the design philosophy, technical barriers, and performance evaluation of such an engine, as well as its current and potential commercial applications. Feedbacks and feature requests from users, which greatly influence our future work, are also addressed.
Music information retrieval research and its context at the University of Waikato
Authors: Bainbridge David 
Published: May 2004

AbstractThis article describes the digital music library work at the University of Waikato, New Zealand. At the heart of the project is a music information retrieval workbench for evaluating algorithms and performing experiments used in conjunction with four datasets of symbolic notation ranging from contemporary to classical pieces. The outcome of this experimentation is woven together with strands from our larger digital library project to form the Web‐based music digital library MELDEX (short for melody index). An overview of the workbench software architecture is given along with a description of how this fits the larger digital library design, followed by several examples of MELDEX in use.
Vorgespannter Stahlbeton
Authors: Buschmeyer Wilhelm , Fastabend Michael 
Published: May 2004

AbstractIm Beitrag wird ein Überblick über das neue Regelwerk für die Bemessung und Konstruktion vorgespannter Betonbauwerke mit internen Spanngliedern ohne Verbund gegeben. Für die Auslegung derartiger Tragwerke wird ein Entwurfskonzept zur Sicherstellung hoher Dauerhaftigkeitsanforderungen während der vorgesehenen Nutzungsdauer mit Schwerpunkt auf dem Gebiet des Flachdecken‐, Brücken‐ und Behälterbaus diskutiert. Empfehlungen zur Wahl eines hierfür geeigneten Vorspanngrades werden im Zusammenhang mit Ausführungsbeispielen vorgestellt.
Verankerung externer Spannglieder an Querträgerscheiben
Authors: Hegger Josef , Neuser Jens U. 
Published: May 2004

AbstractDie sorgfältige Bemessung und Konstruktion von Verankerungs‐ und Umlenkstellen ist Voraussetzung für sichere und dauerhafte Brückenbauwerke mit externer Vorspannung. Das Tragverhalten der Verankerungskonstruktionen läßt sich mit herkömmlichen Stabwerkmodellen beschreiben. Es wird ein Bemessungsmodell mit einfachen Gleichungen bzw. Diagrammen für Querträgerscheiben hergeleitet und beispielhaft angewendet.
Zur Ermittlung des Böenreaktionsfaktors bei turbulenzerregten Bauwerksschwingungen unter Windlast
Authors: Rosemeier Gustav‐Erich 
Published: May 2004

AbstractBei schwingungsanfälligen Bauwerken ist die Ermittlung des Böenreaktionsfaktors von entscheidender Bedeutung. Bei großen Schwingungsamplituden kann durch die aktivierte aerodynamische Dämpfung eine erhebliche Vergrößerung der Gesamtdämpfung einer Struktur eintreten. Hierfür wird eine einfache Schätzformel bereitgestellt. Weiterhin wird nachgewiesen, daß der Böenreaktionsfaktor oft maximal den Wert eines einmaligen Impulses annimmt, bei dem die Windgeschwindigkeit in kurzer Zeit von sehr kleinen Werten auf den Maximalwert springt. Der Normentwurf E‐DIN 1055‐4: 2001‐03 überschätzt den quasistatischen Anteil der Windlast bei der Berechnung des Böenreaktionsfaktors. Deshalb wird hier ein Verbesserungsvorschlag erläutert, der mit den eigenen Parameterstudien besser übereinstimmt.
Conformational studies on enkephalins using the MOLS technique
Authors: Vengadesan K. , Gautham N. 
Published: May 2004

AbstractConformational studies of two linear enkephalin molecules, Met‐enkephalin and Leu‐enkephalin, have been carried using the mutually orthogonal Latin squares (MOLS) technique with the ECEPP/3 force field. This technique was developed recently in our laboratory to perform an unbiased search of the conformational space of peptides and to locate low energy conformations. The present study identified all the folds predicted by other studies, and in addition picked up other energetically favorable structures. The results suggest that the peptide backbone exists as a mixture of folded and unfolded forms (approximately 50% each). The study also provides information on the distribution of the low energy conformations that we have classified on the basis of structural motifs, backbone hydrogen‐bonding patterns, and root mean square deviations in atomic positions. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Ultrabright fluorescein‐labeled antibodies near silver metallic surfaces
Authors: Lakowicz Joseph R. , Malicka Joanna , Huang Jun , Gryczynski Zygmunt , Gryczynski Ignacy 
Published: May 2004

AbstractFluorescein‐labeled antibodies are widely used in clinical assays and fluorescence microscopy. The fluorescent signal per labeled antibody is limited by fluorescein self‐quenching, which occurs when the antibody is heavily labeled with multiple fluoresceins. We examined immunoglobulin G (IgG) when labeled with 0.7 to about 30 fluoresceins per antibody molecule. The extent of self‐quenching was decreased, and the signal increased, when the labeled antibody was in close proximity to metallic silver particles. Time‐resolved measurements showed that the intensity increase was due in part to a silver‐induced increase in the radiative decay rate. These results suggest the use of labeled antibodies conjugated to silver particles as ultrabright probes for imaging or analytical applications. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Photophysical and Phototoxic Properties of the Antibacterial Fluoroquinolones Levofloxacin and Moxifloxacin
Authors: Viola Giampietro , Facciolo Laura , Canton Marcella , Vedaldi Daniela , Dall'Acqua Francesco , Aloisi Gian Gaetano , Amelia Matteo , Barbafina Arianna , Elisei Fausto , Latterini Loredana 
Published: May 2004

AbstractTwo antibacterial fluoroquinolones, levofloxacin and moxifloxacin, were investigated to evaluate their photophysical properties and to explore the mechanism of their phototoxicity. Photophysical experiments were carried out in aqueous solution by stationary and time‐resolved fluorimetry, and by laser flash photolysis, to obtain information on the various decay pathways of the excited states of the drugs and on transient species formed upon irradiation. The results obtained show that levofloxacin is able to photosensitize red blood cell lysis in an oxygen‐independent way and induce a high decrease in cell viability after UVA irradiation, although to a lesser degree than the racemic mixture ofloxacin. Moxifloxacin, which is an 8‐MeO‐substituted fluoroquinolone, is less phototoxic than the other compounds. Cellular phototoxicity was inhibited by the addition of superoxide dismutase, catalase, and free radical and hydroxyl radical scavengers (BHA, GSH, mannitol, and DMTU), indicating the involvement of superoxide anion and/or a radical mechanism in their cytotoxicity. A good correlation was observed between lipid peroxidation, protein photodamage, and cellular phototoxicity, indicating that test compounds exert their toxic effects mainly in the cellular membrane. Experiments carried out on pBR322 DNA show that these derivatives do not significantly photocleave DNA directly, but single‐strand breaks were evidenced after treatment of photosensitized DNA by two base‐excision‐repair enzymes, and Endo III.
Chemical Biology of the Sugar Code
Authors: Gabius Hans‐Joachim , Siebert Hans‐Christian , André Sabine , Jiménez‐Barbero Jesús , Rüdiger Harold 
Published: May 2004

AbstractA high‐density coding system is essential to allow cells to communicate efficiently and swiftly through complex surface interactions. All the structural requirements for forming a wide array of signals with a system of minimal size are met by oligomers of carbohydrates. These molecules surpass amino acids and nucleotides by far in information‐storing capacity and serve as ligands in biorecognition processes for the transfer of information. The results of work aiming to reveal the intricate ways in which oligosaccharide determinants of cellular glycoconjugates interact with tissue lectins and thereby trigger multifarious cellular responses (e.g. in adhesion or growth regulation) are teaching amazing lessons about the range of finely tuned activities involved. The ability of enzymes to generate an enormous diversity of biochemical signals is matched by receptor proteins (lectins), which are equally elaborate. The multiformity of lectins ensures accurate signal decoding and transmission. The exquisite refinement of both sides of the protein–carbohydrate recognition system turns the structural complexity of glycans—a demanding but essentially mastered problem for analytical chemistry—into a biochemical virtue. The emerging medical importance of protein–carbohydrate recognition, for example in combating infection and the spread of tumors or in targeting drugs, also explains why this interaction system is no longer below industrial radarscopes. Our review sketches the concept of the sugar code, with a solid description of the historical background. We also place emphasis on a distinctive feature of the code, that is, the potential of a carbohydrate ligand to adopt various defined shapes, each with its own particular ligand properties (differential conformer selection). Proper consideration of the structure and shape of the ligand enables us to envision the chemical design of potent binding partners for a target (in lectin‐mediated drug delivery) or ways to block lectins of medical importance (in infection, tumor spread, or inflammation).
Classifying Enzymes from Selectivity Fingerprints
Authors: Grognux Johann , Reymond Jean‐Louis 
Published: May 2004

AbstractFingerprints of lipases and esterases have been recorded by using an array of chiral fluorogenic aliphatic esters of increasing chain length (C4–C16). Classification of the enzyme series was carried out with selectivity data by clustering and principal component analysis (PCA). Enzymes were classified on the basis of selectivity for chain length (C4–C6 vs. C10–C16) and of middle‐chain‐length (C8–C10) reactivity. A minimum set of nine substrates was defined by cluster analysis of relative reactivities of each substrate for the different enzymes. This selectivity‐based analysis is general. It does not require a common reference substrate to react with all enzymes or vice versa, and is independent of knowing the exact concentration of active protein in the enzyme samples.
A Powerful Antiradiation Compound Revealed by a New High‐Throughput Screening Method
Authors: Meunier Stéphane , Desage‐El Murr Marine , Nowaczyk Stéphanie , Le Gall Thierry , Pin Serge , Renault Jean‐Philippe , Boquet Didier , Créminon Christophe , Saint‐Aman Eric , Valleix Alain , Taran Frédéric , Mioskowski Charles 
Published: May 2004

AbstractWe present a new high‐throughput screening method for the selection of powerful water‐soluble antiradiation compounds. This method, which uses conventional immunoassay techniques, allowed the capacity of a given compound to protect thymidine from irradiation to be evaluated. By applying this assay to an antioxidant library, we showed for the first time that norbadione A, a well‐known mushroom pigment, has pronounced atypical antiradiation properties.
Functional Evaluation of Carbohydrate‐Centred Glycoclusters by Enzyme‐Linked Lectin Assay: Ligands for Concanavalin A
Authors: Köhn Maja , Benito Juan M. , Ortiz Mellet Carmen , Lindhorst Thisbe K. , García Fernández José M. 
Published: May 2004

AbstractThe affinities of the mannose‐specific lectin concanavalin A (Con A) towards D‐glucose‐centred mannosyl clusters differing in the anomeric configuration of the monosaccharide core, nature of the bridging functional groups and valency, have been measured by a competitive enzyme‐linked lectin assay. Pentavalent thioether‐linked ligands (5 and 7) were prepared by radical addition of 2,3,4,6‐tetra‐O‐acetyl‐1‐thio‐α‐D‐mannopyranose to the corresponding penta‐O‐allyl‐α‐ or ‐β‐D‐glucopyranose, followed by deacetylation. The distinct reactivity of the anomeric position in the D‐glucose scaffold was exploited in the preparation of a tetravalent cluster (10) that keeps a reactive aglyconic group for further manipulation, including incorporation of a reporter group or attachment to a solid support. Hydroboration of the double bonds in the penta‐O‐allyl‐α‐D‐glucopyranose derivative and replacement of the hydroxy groups with amine moieties gave a suitable precursor for the preparation of pentavalent and 15‐valent mannosides through the thiourea‐bridging reaction (17 and 20, respectively). The diastereomeric 1‐thiomannose‐coated clusters 5 and 7 were demonstrated to be potent ligands for Con A, with IC50 values for the inhibition of the Con A–yeast mannan association indicative of 6.4‐ and 5.5‐fold increases in binding affinity (valency‐corrected values), respectively, relative to the value for methyl α‐D‐mannopyranoside. The tetravalent cluster 10 exhibited a valency‐corrected relative lectin‐binding potency virtually identical to that of the homologous pentavalent mannoside 7. In sharp contrast, replacement of the 1‐thiomannose wedges of 5 with α‐D‐mannopyranosylthioureido units (17) virtually abolished any multivalent or statistic effects, with a dramatic decrease of binding affinity. The 15‐valent ligand 20, possessing classical O‐glycosidic linkages, exhibited a twofold increase in lectin affinity relative to the penta‐O‐(thioglycoside) 5; it is less efficient based on the number of mannose units. The results illustrate the potential of carbohydrates as polyfunctional platforms for glycocluster construction and underline the importance of careful design of the overall architecture in optimising glycocluster recognition by specific lectins.
Comparative Analysis of Putative Agonist‐Binding Modes in the Human A1 Adenosine Receptor
Authors: Gutiérrez‐de‐Terán Hugo , Pastor Manuel , Centeno Nuria B. , Åqvist Johan , Sanz Ferran 
Published: May 2004

AbstractA recent study reported a model of the human A1 adenosine receptor and its agonist binding site, proposing two putative binding modes in the same binding site for the natural agonist, adenosine. The present work investigates the flexibility of this binding site by exhaustive exploration with the natural agonist and with three other adenosine derivatives: N6‐cyclopentyladenosine (CPA), 2‐chloro‐N6‐cyclopentyladenosine (CCPA), and 5′‐N‐ethylcarboxamidoadenosine (NECA). Our aim was to find a common binding mode for agonists that would explain the role in the binding process of the different substitutions allowed at the 2, N6, and 5′ positions of adenosine. This problem was addressed through docking simulations, molecular dynamics studies, and estimations of the ligand‐binding free energy with both the AUTODOCK scoring function and the linear interaction energy (LIE) approach. The results point to a single receptor‐binding position that explains the effects of the different chemical modifications on the adenosine derivatives considered here.
Two‐Dimensional Multiarray Formation of Hepatocyte Spheroids on a Microfabricated PEG‐Brush Surface
Authors: Otsuka Hidenori , Hirano Akihiro , Nagasaki Yukio , Okano Teruo , Horiike Yasuhiro , Kataoka Kazunori 
Published: May 2004

AbstractA two‐dimensional microarray of ten thousand (100×100) hepatocyte heterospheroids, underlaid with endothelial cells, was successfully constructed with 100 μm spacing in an active area of 20×20 mm on microfabricated glass substrates that were coated with poly(ethylene glycol) brushes. Cocultivation of hepatocytes with endothelial cells was essential to stabilize hepatocyte viability and liver‐specific functions, allowing us to obtain hepatocyte spheroids with a diameter of 100 μm, functioning as a miniaturized liver to secret albumin for at least one month. The most important feature of this study is that these substrates are defined to provide an unprecedented control of substrate properties for modulating cell behavior, employing both surface engineering and synthetic polymer chemistry. The spheroid array constructed here is highly useful as a platform of tissue and cell‐based biosensors and detects a wide variety of clinically, pharmacologically, and toxicologically active compounds through a cellular physiological response.
Light‐Activated Transcription and Repression by Using Photocaged SERMs
Authors: Shi Youheng , Koh John T. 
Published: May 2004

AbstractRecently developed methods to regulate the spatial and temporal patterning of genes in a light‐directed manner hold promise as powerful tools for exploring the function of genes that act through their unique spatiotemporal patterning. To further explore the application of photocaged ligands of nuclear receptors to control gene expression patterning, the actions of photocaged analogues of selective estrogen‐receptor modulators (SERMs) have been evaluated. Photocaged derivatives of hydroxytamoxifen (NB‐Htam) and guanidine tamoxifen (NB‐Gtam) have been synthesized that selectively antagonize ERα‐ and ERβ‐mediated transcription at classic estrogen response elements (EREs) in response to light. When present only intracellularly, Htam and Gtam provide a similar transient repression response. When SERMs are allowed to diffuse out of the cell, transcription is recovered at a similar rate for Htam and Gtam (6.4 and 5.6 h−1), but is notably faster than is observed with the covalently binding SERM tamoxifen aziridine (Taz) (3.8 h−1). This suggests that the duration of agonist action is controlled by ligand off‐rates/diffusion and not by receptor turnover. Gtam activates ERβ‐mediated transcription at AP1 sites in a similar way to what has previously been reported for Htam. NB‐Gtam and NB‐Tam provide a light‐activated transcription response at AP1‐driven reporters, thus illustrating the unique ability of photocaged SERMs to simultaneously mediate light‐activated transcription and repression.
A Novel Bis‐aziridinylnaphthoquinone with Anti‐Solid Tumor Activity in which Induced Apoptosis is Associated with Altered Expression Of Bcl‐2 Protein
Authors: Huang Sheng‐Tung , Tsai Hsin‐Da , Kuo Hsien‐Shou , Yang Yu‐Ping , Peng Yi‐Chen , Lin Yuh‐Ling 
Published: May 2004

AbstractAziridine‐containing compounds have been of interest as anticancer agents since the late 1970s. The design, synthesis, and study of aziridinylnaphthoquinone analogues to obtain compounds with enhanced activity/toxicity profiles are an ongoing research effort in our group. A series of bis‐aziridinylnaphthoquinone derivatives has been prepared, and the cytotoxic activities of these synthetic bis‐aziridinylnaphthoquinone derivatives has been investigated. The synthetic derivatives displayed significant cytotoxicity against human carcinoma cell lines and weak cytotoxic activities against skin fibroblasts (SF). The bis‐aziridinylnaphthoquinone 1 c was the most effective of the tested analogues at reducing the viability of Hep2 cells, with an LD50 value of 5.23 μM, and also exhibited weak cytotoxic activity against SF cells, with an LD50 value of 54.12 μM. The DNA alkylation and DNA interstrand cross‐linking abilities of 1 c were also investigated. Bis‐aziridinylnaphthoquinone 1 c was an effective agent for alkylation of DNA after chemical reduction in vitro, and its bifunctional alkylating moieties were able to cross‐link DNA. We also report here our efforts to determine direct antitumor effects of 1 c on Hep2 cells. Growth arrest in Hep2 cells was preceded by early induction of G2‐M cell cycle arrest at 0.75 μM of 1 c after culture for 24 h, and was then followed by apoptosis after 60 h. This was associated with decreased expression of antiapoptotic bcl2 protein (by 78 %) upon culture with 3.0 μM of 1 c after 60 h. Our results suggest that 1 c is a novel antitumor aziridinylnaphthoquinone with therapeutic potential against solid tumors.
Reactions of Substituted (1,3‐Butadiene‐1,4‐diyl)magnesium, 1,4‐Bis(bromomagnesio)butadienes and 1,4‐Dilithiobutadienes with Ketones, Aldehydes and PhNO To Yield Cyclopentadiene Derivatives and N‐Ph Pyrroles by Cyclodialkenylation
Authors: Fang Hongyun , Li Guotao , Mao Guoliang , Xi Zhenfeng 
Published: May 2004

Abstract1,4‐Dilithiobutadiene derivatives 1, 1,4‐bis(bromomagnesio)butadiene derivatives 2 and metallacyclic (1,3‐butadiene‐1,4‐diyl)magnesium reagents 3 were prepared and their reactions with ketones, aldehydes, and PhNO were investigated. Multiply substituted cyclopentadienes and N‐Ph pyrroles were formed by unprecedented reaction conditions. The carbonyl group of aldehydes and ketones was deoxygenated during the reaction and behaved formally as a one‐carbon unit; the NO moiety of PhNO was cleaved to afford N‐Ph pyrrole derivatives. Furthermore, different reactivities among these three types of reagents 1, 2 and 3 were revealed. The 1,4‐dilithium reagents 1 readily reacted with both aldehydes and ketones; the 1,4‐dimagnesium reagents 2 reacted with aldehydes, but not ketones; the metallacyclopentadiene reagents of magnesium 3 showed higher reactivity and did react with ketones.