bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stabilization of somatropin by heparin
Authors: Zamiri Camellia , Groves Michael J 
Published: April 2005

Abstract
Somatropin, human growth hormone (hGH), is an unstable protein, posing challenging problems for its formulation and long-term stability. Since hGH formed insoluble adducts with heparin our aim was to evaluate heparin as a stabilizing agent for the drug. These adducts were characterized by particle diameter, tertiary structure variations and release studies. Studies were also carried out to determine the stability of hGH in the presence and absence of heparin by an interfacial denaturation method and real-time stability studies by measuring hGH activity and particle diameter. Moreover, biological activity of hGH and hGH/UH (unfractionated heparin) adducts was identified by daily subcutaneous injections to hypophysectomized rats. There was a decrease in mean hydrodynamic particle diameter of hGH/UH adducts with increased pH (54.4 to 12.2 nm from pH 3 to pH 7) indicating that the adducts were either dissociating or dissolving at high pH. Furthermore, second-derivative spectroscopy indicated that complexation of hGH with heparin did not cause a major disruption in the tertiary structure of hGH but decreased the hydrophilic environment around the tyrosine residues. Release of hGH from hGH/UH adducts was pH and ionic strength dependent with the highest release at pH 8 (93%) and lowest release at pH 3 (0%) over the first hour. Interfacial denaturation methods indicated that vortex agitation over 120 s resulted in no change in the optical density of hGH/UH adducts compared with a substantial increase for hGH alone at pH 6.8. Real-time stability studies over 93 days demonstrated that hGH/UH adducts at both pH 3 and 7 with an excess of heparin produced the highest percent of active hGH remaining in the solution at 4°C and 37°C. The higher stability of hGH/UH adducts with excess heparin compared with the stoichiometric ratio was also confirmed by particle size measurements during storage. The biological activity of these adducts was comparable with hGH alone by weight-gain studies in hypophysectomized rats. The findings suggest the value of using hGH/heparin adducts to stabilize the protein.
S-adenosyl-l-methionine: transcellular transport and uptake by Caco-2 cells and hepatocytes
Authors: McMillan J M , Walle U K , Walle T 
Published: April 2005

Abstract
S-adenosyl-l-methionine (SAMe) is an endogenous molecule that is known to be protective against hepatotoxic injury. Although oral SAMe appears to be absorbed across the intestinal mucosa, its systemic bioavailability is low. The reason for this is unknown. Using the Caco-2 cell culture model for enterocyte absorption, we determined the mode by which SAMe is transported across this cell monolayer. We also determined the extent it is taken up by both Caco-2 cells and hepatocytes. In Caco-2 cells transport was observed in both apical to basolateral and basolateral to apical directions. The apparent permeability coefficients (Papp) appeared to be concentration independent and were similar in both directions (0.7 times 10−6 and 0.6 times 10−6 cms−1, respectively), i.e. identical to that of the paracellular transport marker mannitol (0.9 times 10−6 and 0.7 times 10−6 cms−1). This mode of transport was supported by a four-fold increase in the Papp for SAMe transport in Ca++-free buffer. Cellular uptake of SAMe was examined in both Caco-2 cells and cultured rat hepatocytes. Uptake by hepatocytes was not saturable in a concentration range of 0.001–100 μm. Accumulation by both cell types was very low, with a cell:medium ratio at equilibrium of only 0.2–0.5. This low cell accumulation supports the finding of paracellular transport as the only mode of cell membrane transport. Increased hepatocellular protection for SAMe may be accomplished by converting SAMe to a more lipid-soluble prodrug.
In-situ-Messung von Strom- und Spannungsverläufen in Mikrowellentransistoren (In-situ Measurement of Current and Voltage Waveforms in Microwave-Transistors)
Authors: Arthaber Holger 
Published: April 2005

Abstract
Dieser Artikel stellt ein Messsystem vor, welches über indirekte Messung eine Echtzeitdarstellung von Strom und Spannung am aktiven Kanal eines nichtlinear betriebenen Mikrowellentransistors erlaubt. Zusätzlich ist es möglich, die Lastimpedanzen sowohl bei der Ausgangsfrequenz als auch bei den durch die Nichtlinearität entstehenden Oberwellen getrennt voneinander einzustellen. Um die Messung von Transistoren in hocheffizienten Betriebspunkten zu ermöglichen, ist eine nahezu perfekte Reflexion der Oberwellen erforderlich, welche mittels „aktiver Lasten“ erzielt wird. Die Funktion des Aufbaus wird mit Messungen an einem pHEMT-Mikrowellentransistor gezeigt.
Einzelelektronen-Schaltungen für Anwendungen in der Metrologie (Single-Electron Circuits for Metrological Applications)
Authors: Scherer Hansjörg 
Published: April 2005

Abstract
Die elektrische Abstoßung zwischen einzelnen Elektronen manifestiert sich in ultrakleinen metallischen Tunnelkontakt-Schaltungen als makroskopisch beobachtbarer Effekt, wenn deren Coulomb-Wechselwirkung auf der Energieskala dominiert. Die resultierenden Einzelladungseffekte erlauben eine gezielte Manipulation einzelner Ladungsquanten und damit einzigartige Anwendungen für die elektrische Metrologie. Zu den metrologisch interessanten Einzelelektronen-Bauelementen zählen Elektrometer, die den Nachweis kleinster elektrischer Ladungen in der Größenordnung von Bruchteilen der Elementarladung ermöglichen, und die so genannte Einzelelektronenpumpe, die den getakteten Transfer von Ladungsquanten durch eine Schaltung und damit prinzipiell die Realisierung eines Quantenstromnormals gestattet. Die Kombination beider Schaltungstypen ermöglicht schließlich die Implementierung eines neuartigen Kapazitätsstandards. Dieser Beitrag gibt einen Überblick über die genannten Themenfelder und geht auf den aktuellen Stand der metrologischen Anwendung an der PTB ein.
Monolithische Korrelationsempfänger für optische Abstandsmessung (Integrated Correlation Receivers for Runtime Based Optical Distance Measurement)
Authors: Oberhauser Klaus , Nemecek Alexander , Zimmermann Horst 
Published: April 2005

Abstract
Durch Laufzeitmessung von Licht können diffus reflektierende räumliche Objekte mit integrierten optischen Abstandssensoren sehr schnell vermessen werden. Mögliche Anwendungsgebiete sind z.B. Sicherheitsanwendungen im Automobil. Sehr kurze Laufzeiten (ns) sowie geringe optische Empfangsleistung (nW), resultierend aus der notwendigen Augensicherheit, stellen hohe Anforderungen an den Empfänger, denen die integrierten PIN-Photodioden durch hohen Wirkungsgrad (R=0.36A/W @ 660nm) bei hoher Detektorbandbreite (f
3dB=1.35GHz) genügen. Anhand zweier realisierter Sensorkonzepte werden unterschiedliche Funktionsweisen demonstriert: interne und externe Signalkorrelation des Photodetektors. Der Laboraufbau, bestehend aus modulierter Lichtquelle (Laser), Optik, Sensorchip, Ansteuerlogik und Messauswertung, ermöglicht durch Mittelung Messgenauigkeiten von 1% für Abstände bis zu 3.7m. Die optoelektronischen integrierten Schaltungen (OEICs) sind in einem modifizierten 0,6-μm-BiCMOS-Prozess hergestellt.
Nondisjunction
Authors: Lamb Neil E. 
Published: April 2005

Abstract
Nondisjunction is the improper segregation of chromosomes during either meiotic or mitotic cell divisions. Mitotic nondisjunction is commonly observed in cancer, while nondisjunction during meiosis results in gametes that are chromosomally unbalanced. If an unbalanced gamete participates in fertilization, the resulting embryo will be aneuploid, with either one chromosome too many (trisomy) or one chromosome too few (monosomy). Because these embryos are generally inviable, nondisjunction in humans has serious clinical consequences. Although monosomic conditions appear to result in early embryonic lethality, most trisomic conditions are compatible with at least some fetal development. DNA marker studies indicate that nondisjunction errors in the female during the first stage of meiosis predominate among nearly all trisomic conditions. In addition, most, if not all, human trisomies are affected by increasing maternal age. Very little is understood regarding the mechanisms that underlie this age effect. Recently, altered genetic recombination has been identified as the first molecular correlate of human nondisjunction. It appears likely that the risk of nondisjunction posed by altered recombination varies among the chromosomes. Other risk factors for nondisjunction have been suggested, but to date, none have been conclusively proven. As a result, an understanding of the molecular mechanisms for nondisjunction and the maternal age effect remains elusive.
Cytogenetic analysis of lymphomas
Authors: Horsman Douglas E. 
Published: April 2005

Abstract
Microscopic analysis of the chromosomes in the malignant cells of lymphoma specimens has provided useful information for clinical management of patients and has provided targets for molecular genetic research efforts to identify the genes that are deregulated during the development and progression of this type of cancer. The use of fluorescent‐dye‐labeled DNA probes specific for these genes has facilitated the detection of disease‐specific chromosome rearrangements in fresh and archived clinical specimens. This type of cancer genetic analysis will become an increasingly important tool for the laboratory investigation and clinical management of malignant lymphoma.
Noncoding
RNAs
in mammals
Authors: Ravasi Timothy , Hume David A. 
Published: April 2005

Abstract
Transcripts that lack any protein‐coding potential represent at least half of the identified elements transcriptome. We review the evidence for the existence of such transcripts in the mammalian transcriptome, and argue that there may be many more noncoding RNAs (ncRNAs) still to be discovered. Relatively few ncRNA “genes” have been ascribed a function based upon mutation analysis. The review discusses possible roles of ncRNAs as cis‐acting and trans‐acting elements in epigenetic transcriptional control, including monoallelic gene silencing and imprinting. We also consider the evidence that the production of ncRNAs is a common feature of transcriptional enhancers.
CreatingLDmaps of the genome
Authors: Collins Andrew , Ennis Sarah 
Published: April 2005

AbstractPatterns of linkage disequilibrium (LD) are determined to a substantial extent by recombination. This suggests that an LD map of the genome, analogous to the linkage map, would be a valuable tool. One approach to constructing such a map, which models the decline of LD between adjacent single nucleotide polymorphisms, recovers map distances, which show a very high correlation with the corresponding linkage map distances. Furthermore, the apparent colocalization of recombination hot spots in all populations suggests that a standard “cosmopolitan” LD map is achievable. There are evident benefits in terms of increased power and resolution for mapping when a disease determinant is localized on a linkage disequilibrium map. Further power increases might be achieved by combining LD maps with the analysis of short haplotypes.
Genotyping technology: the present and the future
Authors: Kwok Pui‐Yan , Chan Ting‐Fung 
Published: April 2005

Abstract
Genotyping technologies for single nucleotide polymorphisms (SNPs) have matured greatly in recent years. Although a universal method that meets all genotyping needs does not exist, many innovative, robust, high‐throughput, and cost‐effective approaches have been developed. The enormous interest in using SNPs as markers for mapping complex disease genes, and their other applications in diagnostics and pharmacogenomics will continue to drive the improvement of genotyping methods. In this article, we discuss several directions being taken for further development of genotyping technologies.
MicroarrayCGH
Authors: Smirnov Denis A. , Cheung Vivian G. 
Published: April 2005

AbstractComparative genomic hybridization (CGH) is a molecular cytogenetic method for detection of chromosomal abnormalities. Traditionally, normal metaphase chromosomes were used as substrates for CGH analysis. Recent advances in microarray technology and developments in the human genome project allow substitution of metaphase chromosomes with collections of arrayed genomic clones, cDNA clones, or oligonucleotides. When combined with such microarrays, CGH can be used for genome‐wide high‐resolution characterization of cytogenetic imbalances. This review focuses on recent advances and remaining challenges in manufacturing genomic microarrays and using them for identification of chromosomal abnormalities by microarray CGH.
The yeast interactome
Authors: Uetz Peter , Grigoriev Andrei 
Published: April 2005

Abstract
The yeast proteome and its interactome (that is, the sum of all protein interactions) are the best studied of all organisms. Currently, there are about 3000 verified protein interactions and several thousand nonverified interactions known in yeast. Independent studies estimated that there may be more than 30 000 interactions in yeast although most estimates rather suggest 15 000–25 000. It remains unknown how many of these interactions are really essential. The average yeast protein appears to have about five interactions but this number may represent an overestimate because many proteins of yet unknown function exhibit fewer interactions. Nevertheless, most proteins can be connected in a huge network of interactions. The protein interaction network of yeast is highly dynamic although there are 1500 or more proteins involved in several hundred stable complexes. The dynamics and regulation of protein interaction networks, for example, by protein modifications, are only now being explored. There are no clear physical properties of a yeast protein that predicts its interaction properties but several protein families (such as proteins involved in RNA splicing) seem to be much more highly connected than others (such as metabolic enzymes).
Biochemistry of protein complexes
Authors: Séraphin Bertrand 
Published: April 2005

Abstract
Following the determination of the full sequence of a genome of interest, functional analyses are directed to the understanding of the functions of the polypeptides that it encodes. Elucidation of the network of protein–protein interaction occurring in the cell under study is then of the highest importance, as the formation of such protein complexes is at the hearth of most reactions governing the regulation of the main cellular functions. Several strategies have been developed for the detection of protein interactions. In this report, the rationale behind the methods used for the biochemical characterization of protein complexes is described and the limitations of such approaches are discussed. Examples of various methods that have been used in the biochemical analysis of protein complexes are provided. The diverse applications of protein purifications are described and the results obtained in large‐scale analyses of protein complexes are discussed.
TheC.elegansinteractome project
Authors: Hill David E. , Cusick Michael E. , Vidal Marc 
Published: April 2005

AbstractThe long‐term goal of the research described in this chapter is to understand how macromolecular networks control animal development and how changes in such networks can lead to human diseases. Recently released protein–protein interaction or “interactome” maps for multicellular organisms have helped us to start imagining how complex cellular networks are organized.
Energy transfer–based approaches to study
G
protein–coupled receptor dimerization and activation
Authors: Jockers Ralf , Bouvier Michel , Marullo Stefano 
Published: April 2005

Abstract
During the past several years, energy transfer–based techniques have become quite popular to study G protein–coupled receptors and the dynamic processes that follow their activation. This review will highlight a number of important biological questions in the field of GPCR biology that have been addressed using these approaches.
Photobleaching (
FRAP
/
FLIP
) and dynamic imaging
Authors: Banting George 
Published: April 2005

Abstract
The techniques of Fluorescence Recovery After Photobleaching (FRAP) and Fluorescence Loss In Photobleaching (FLIP) both provide ways to monitor the movement of fluorescently tagged proteins within live cells. The development of genetically encoded fluorescent tags (e.g., green fluorescent protein, GFP) has made FRAP and FLIP accessible to researchers with a broad range of interests and technical expertise. This review outlines the principles underlying FRAP and FLIP, highlights the type of information that may be obtained using these techniques, and points out some caveats that need to be considered when using them.
Glycoproteomics
Authors: Dwek Miriam V. , Mills Philippa 
Published: April 2005

Abstract
Many diverse functions have been attributed to glycans on proteins and increasingly there is a need to characterize glycan structures. This article describes the laboratory approaches that are currently used for the analysis of glycans on proteins and considers Bioinformatics tools for the identification of putative protein glycosylation sites as well as for the analysis of the glycans themselves.
Peptidases, families, and clans
Authors: Rawlings Neil D. , Barrett Alan J. 
Published: April 2005

Abstract

Peptidases (all proteolytic enzymes) are classified in a hierarchical system on the basis of evolutionary relationships. An identifier is assigned to each distinctive peptidase, and for each amino acid sequence, properties including the limits of the peptidase unit and the positions of the active site residues are recorded. The peptidase unit is the part of the molecule directly responsible for peptidase activity, and sequence comparisons are made only with this to exclude false‐positive matches with nonpeptidase domains. The peptidases are grouped in families, each of which contains a type‐example peptidase and all the peptidases that can be shown to be related to it either directly or indirectly (transitively). Families that show evidence of being homologous are grouped together in a clan, so each clan is intended to contain the modern‐day representatives of a single origin of peptidases. The evidence for homology of families comes from similarities in protein fold as well as the arrangement of active site residues and motifs in the sequence. A clan may contain just a single family with a unique structure. The classification forms the logical structure of the MEROPS database (
merops.sanger.ac.uk
), which also includes a summary, structural representation, and bibliography for each peptidase, family, and clan, a sequence alignment for each family and clan, and a tree for each family.
The
PIR
S
uper
F
amily (
PIRSF
) classification system
Authors: Barker Winona C. , Mazumder Raja , Nikolskaya Anastasia N. , Wu Cathy H. 
Published: April 2005

Abstract

Protein family classification provides effective means for large‐scale genome annotation and biological knowledge discovery based on the information embedded within families of homologous sequences and their structures. The Protein Information Resource (PIR) developed the PIRSF (SuperFamily) system,
a network classification system based on evolutionary relationship of full‐length proteins
, to facilitate the propagation and standardization of protein annotation. Sequence analysis and protein classification based on full‐length proteins, including the preservation of domain architecture, can lead to educated predictions for both generic biochemical and specific biological functions. The multiple levels of sequence diversity, from superfamilies to subfamilies, reflect different degrees of functional granularity and, thereby, allow more accurate propagation of annotation and the development of standard protein nomenclature and ontology. The PIRSF database is integrated with other family, function, and structural classification schemes, and is accessible at
http://pir.georgetown.edu/pirsf/
for report retrieval and sequence classification.
Large complexes and molecular machines by electron microscopy
Authors: Plitzko J. M. , Engelhardt H. 
Published: April 2005

Abstract
Cryo‐electron tomography has the unique potential of visualizing the structure of large protein complexes in isolated preparations at high resolution and in their natural context, in unperturbed cells. Tomograms of vitrified cells are essentially three‐dimensional images of their entire proteome. They contain the information of the spatial relationship of macromolecules, their interactions, and reveal the assembly of macromolecular machines that are only stable in vivo. Here, we present a brief survey of the principles and developments of cryo‐electron microscopy and image reconstruction.
Genome maps and their use in sequence assembly
Authors: Dear Paul H. 
Published: April 2005

Abstract
Genome maps give the location of defined sequence features in the genome and serve as a framework around which to assemble the complete genome sequence. Without them, the complete assembly of complex genomes purely from the shotgun sequence data is effectively impossible. Here, I summarize the principle methods that are used to make detailed genome maps and the ways in which mapping and sequencing are integrated to produce finished genome sequences.
Eukaryotic regulatory sequences
Authors: Krull Mathias , Wingender Edgar 
Published: April 2005

Abstract
The existence and clustering of particular regulatory sequences is the main determinant of specific gene expression. While the sequences of whole genomes for several species are now available, information on those control elements is relatively sparse. The numerousness of elements in the genome limits experimental identification. In‐depth knowledge on DNA binding sites of transcription factors and their role in regulatory modules will enable genome‐wide in silico site prediction with high sensitivity and specificity. Here we present a short review of the types of regulatory sequences and the computational methods that are applied for their characterization and prediction.
Threading algorithms
Authors: Bienkowska Jadwiga , Lathrop Rick 
Published: April 2005

Abstract
This chapter reviews various algorithms that have been developed for protein structure prediction by threading. Threading algorithms depend on many features of protein sequence and structure representations and not all of them are used by all methods. There is no standard formalism to represent those different features. While providing necessary detail, sometimes the formal notation obscures the core idea of an algorithm. In order to make the core ideas transparent to many readers, we made an effort to adhere to a simple formalism and tried to avoid mathematical formulas. This forced us to omit many details and complete outlines of algorithms, for which the reader is referred to the original literature for a detailed picture.
RNA
secondary structure prediction
Authors: Mathews David H. , Zuker Michael 
Published: April 2005

Abstract
The field of RNA secondary structure prediction matured in the last 10 years with the development of many readily available software packages. The thermodynamic parameters for predicting the free energy of an RNA secondary structure are continuing to be revised on the basis of new experiments. This article reviews the available secondary structure prediction algorithms for both a single sequence and multiple sequences.