bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of inter-administrative domain routing protocols
Authors: Breslau L. , Estrin D. 
Published: October 2004

Policy Routing (PR) is a new area of development that attempts to incorporate policy related constraints on inter-Administrative Domain (AD) communication into the route computation and forwarding of inter-AD packets.
Proposals for inter-AD routing mechanisms are discussed in the context of a design space defined by three design parameters: location of routing decision (i.e., source or hop-by-hop), algorithm used (i.e., link state or distance vector), and expression of policy in topology or in link status. We conclude that an architecture based upon source routing, a link state algorithm, and policy information in the link state advertisements, is best able to address the long-term policy requirements of inter-AD routing. However, such an architecture raises several new and challenging research issues related to scaling.
Performance analysis of FDDI token ring networks: effect of parameters and guidelines for setting TTRT
Authors: Jain Raj 
Published: October 2004

Fiber-Distributed Data Interface (FDDI) is a 100-Mbps Local Area Network (LAN) standard being developed by the American National Standards Institute (ANSI). It uses a timed-token access method and allows up to 500 stations to be connected with a total fiber length of 200 km.
We analyze the performance of FDDI using a simple analytical model and a simulation model. The performance metrics of response time, efficiency, and maximum access delay are considered. The efficiency is defined as the ratio of maximum obtainable throughput to the nominal bandwidth of the network. The access delay is defined as the time it takes to receive a usable token.
The performance of FDDI depends upon several workload parameters; for example; the arrival pattern, frame size, and configuration parameters, such as the number of stations on the ring, extent of the ring, and number of stations that are waiting to transmit. In addition, the performance is affected by a parameter called the Target Token Rotation Time (TTRT), which can be controlled by the network manager. We considered the effect of TTRT on various performance metrics for different ring configurations, and concluded that a TTRT value of 8 ms provides a good performance over a wide range of configurations and workloads.
Evaluation of sense-strand mRNA amplification by comparative quantitative PCR
Authors: Goff Loyal A , Bowers Jessica , Schwalm Jaime , Howerton Kevin , Getts Robert C , Hart Ronald P 
Published: October 2004

Abstract
Background
RNA amplification is required for incorporating laser-capture microdissection techniques into microarray assays. However, standard oligonucleotide microarrays contain sense-strand probes, so traditional T7 amplification schemes producing anti-sense RNA are not appropriate for hybridization when combined with conventional reverse transcription labeling methods. We wished to assess the accuracy of a new sense-strand RNA amplification method by comparing ratios between two samples using quantitative real-time PCR (qPCR), mimicking a two-color microarray assay.

Results
We performed our validation using qPCR. Three samples of rat brain RNA and three samples of rat liver RNA were amplified using several kits (Ambion messageAmp, NuGen Ovation, and several versions of Genisphere SenseAmp). Results were assessed by comparing the liver/brain ratio for 192 mRNAs before and after amplification. In general, all kits produced strong correlations with unamplified RNAs. The SenseAmp kit produced the highest correlation, and was also able to amplify a partially degraded sample accurately.

Conclusion
We have validated an optimized sense-strand RNA amplification method for use in comparative studies such as two-color microarrays.
An unusual case of an ulcerative colitis flare resulting in disseminated intravascular coagulopathy and a bladder hematoma: a case report
Authors: Suskind David L , Murray Karen , Christie Dennis 
Published: October 2004

Abstract
Background
Disorders of coagulation have long been associated with inflammatory bowel disease. Children, as well as adults, with both active and inactive ulcerative colitis have been found to have abnormal coagulation and fibrinolysis. Disseminated intravascular coagulation arises from an overwhelming of the haemostatic regulatory mechanisms leading to an excessive generation of thrombin and a failure of the normal inhibitory pathways to prevent systemic effects of this enzyme. Ulcerative colitis has been associated with disseminated intravascular coagulation in conjunction with septicemia, toxic megacolon and surgery.

Case presentation
A fourteen-year-old boy with a history of poorly controlled ulcerative colitis presented with nonbilious emesis, hematochezia, and hematuria. Laboratory workup revealed disseminated intravascular coagulation. He was placed on triple antibiotics therapy. An infectious workup came back negative. A computerized tomography (CT) scan of the abdomen revealed a marked thickening and irregularity of the bladder wall as well as wall thickening of the rectosigmoid, ascending, transverse, and descending colon. Patient's clinical status remained stable despite a worsening of laboratory values associated with disseminated intravascular coagulation. Patient was begun on high dose intravenous steroids with improvement of the disseminated intravascular coagulation laboratory values within 12 hours and resolution of disseminated intravascular coagulopathy within 4 days. A thorough infectious workup revealed no other causes to his disseminated intravascular coagulation.

Conclusions
The spectrum of hypercoagulable states associated with ulcerative colitis varies from mild to severe. Although disseminated intravascular coagulation associated with ulcerative colitis is usually related to septicemia, toxic megacolon or surgery, we present a case of an ulcerative colitis flare resulting in disseminated intravascular coagulation and a bladder hematoma.
A step ahead: combining protein purification and correct folding selection
Authors: de Marco Ario 
Published: October 2004

AbstractThe success of recombinant protein expression seems unpredictable and even good yields of soluble proteins do not guarantee the correct folding. The search for soluble constructs can be performed by exploiting libraries and speeded up by automation, but these approaches are money and time consuming and the tags used for affinity purification can mask the real stability of the target proteins. The ideal purification protocol would include the structure quality control. A recent paper commented in this article describes a phage-display method to screen for antibodies that are able to re-fold after heat-denaturation and can be selectively affinity-purified only if monodispersed. It turned out that the proteins with high recovery performance after heat-shock were also suitable for efficient recombinant expression.
The pivotal role of cholesterol absorption inhibitors in the management of dyslipidemia
Authors: Al-Shaer Moutasim H , Choueiri Nabil E , Suleiman Ehab S 
Published: October 2004

AbstractElevated low-density lipoprotein (LDL)-cholesterol is associated with a significantly increased risk of coronary heart disease. Ezetimibe is the first member of a new class of selective cholesterol absorption inhibitors. It impairs the intestinal reabsorption of both dietary and hepatically excreted biliary cholesterol. Ezetimibe is an effective and safe agent for lowering LDL-C and non HDL-C. Short term clinical trials have established the role of ezetimibe monotherapy and its use in combination with statins. Furthermore, ezetimibe and statin combination therapy increased the percentage of patients who achieved their LDL-C treatment goal.Studies using surrogate markers of atherosclerosis have suggested a possible role of ezetimibe in combating atherosclerosis. Ezetimibe provides an effective therapeutic strategy for the management of homozygous familial hypercholesterolemia (HoFH) and sitosterolemia. The lack of outcomes and long term safety data is attributed to the relatively recent introduction of this medication.
A Conserved Gβ Binding (GBB) Sequence Motif in Ste20p/PAK Family Protein Kinases
Authors: Leberer E. , Dignard D. , Thomas D.Y. , Leeuw T. 
Published: October 2004

Abstract
Serine/threonine protein kinases of the Ste20p/PAK family are highly conserved from yeast to man. These protein kinases have been implicated in the signaling from heterotrimeric G proteins to mitogen-activated protein (MAP) kinase cascades and to cytoskeletal components such as myosin-I. In the yeast Saccharomyces cerevisiae, Ste20p is involved in transmitting the mating-pheromone signal from the βγ-subunits of a heterotrimeric G protein to a downstream MAP kinase cascade. We have previously shown that binding of the G-protein β-subunit (Gβ) to a short binding site in the non-catalytic carboxy-terminal region of Ste20p is essential for transmitting the pheromone signal. In this study, we searched protein sequence databases for sequences that are similar to the Gβ binding site in Ste20p. We identified a sequence motif with the consensus sequence S S L ϕP L I/V x ϕϕβ (x: any residue; ϕ: A, I, L, S, or T; β: basic residues) that is solely present in members of Ste20p/PAK family protein kinases. We propose that this sequence motif, which we have designated GBB (G̱β̱ ḇinding) motif, is specifically responsible for binding of Gβ to Ste20p/PAK protein kinases in response to activation of heterotrimeric G protein coupled receptors. Thus, the GBB motif is a novel type of signaling domain that serves to link protein kinases of the Ste20p/PAK family to G protein coupled receptors.
Identification of a CpG Island in the Human LRP-2 Gene and Analysis of Its Methylation Status in Parathyroid Adenomas
Authors: Knutson A. , Lillhager P. , Westin G. 
Published: October 2004

Abstract
Methylation of CpG residues in mammalian genomes is a mechanism of vital importance for many cellular functions, which all relate to gene expression. In this study we describe the identification of a CpG island in the 5′-region of the gene encoding human megalin/LRP-2, a receptor capable of binding multiple ligands, which is involved in the regulation of calcium metabolism. Southern blot analysis and genomic bisulfite sequencing revealed that the CpG island is methylated in a non-expressing cell line, largely unmethylated in an expressing cell line and unmethylated in human parathyroid tissue. In addition, we show that artificial methylation of LRP-2 promoter reporter plasmids leads to strong transcriptional repression, in vitro as well as in transfected cells. No evidence for aberrant LRP-2 gene methylation in parathyroid adenomas, in which the LRP-2 protein is generally down-regulated, was found.
Cooperativity of Binding Epitopes and Receptor Chains in the BMP/TGFß Superfamily
Authors: Knaus Petra , Sebald Walter 
Published: October 2004

Abstract
Bone morphogenetic proteins (BMP) are dimeric factors
initiating several distinct signaling cascades by binding to two types of
transmembrane serine/threonine kinase receptors (BRI and BRII), and are thus
regulating several steps in embryonal development and adult tissue homeostasis.
BMP-2 contains two symmetrical pairs of juxtaposed epitopes: the wrist epitope
with high affinity to BRI consists of residues from both BMP-2 monomers, while
the knuckle epitope resembles the low affinity site for BRII and comprises
residues from only one monomer. Here we generated heterodimeric BMP-2 muteins
with one monomer mutant in either epitope I for BRI (eI) or epitope II for BRII
(eII) and the second monomer wild type for receptor interactions (m). These
muteins (B2eI/B2m and B2eII/B2m) were analyzed by biosensor analysis as well as
by measuring their biological activity and compared to their homodimeric forms
(either wild type or mutant). Depletion of only one epitope II results in the
loss of biological activity as measured by alkaline phosphatase (ALP) activity
and Smad induced reportergene assays. However, depletion of only one epitope I
shows a reduction of ALP activity to about 25%, while the activation of the
Smad pathway remained normal. Homomeric muteins are nonfunctional for both Smad
and ALP activation. This suggests that two functional epitopes II have to be
present on one BMP-2 molecule for receptor activation. Futhermore, both
pathways (Smad and ALP) are triggered differently by distinct BMPreceptor
complexes. Heteromeric BMP-2 mutants therefore allow a distinguishable
manipulation of either pathway and thus represent important tools for the
generation of specific BMP-2 antagonists or agonists.
Zinc Induces Apoptosis That Can Be Suppressed by Lanthanum in C6 Rat Glioma Cells
Authors: Haase Hajo , Wätjen Wim , Beyersmann Detmar 
Published: October 2004

AbstractZinc ions have both essential and toxic effects on mammalian cells. Here we report the ability of zinc to act as an inducer of apoptosis in C6 rat glioma cells. Incubation with 150 to 300 M ZnCl2 caused cell death that was characterized as apoptotic by internucleosomal DNA fragmentation, formation of apoptotic bodies, nuclear fragmentation and breakdown of the mitochondrial membrane potential. On the other hand, zinc deprivation by the membrane permeable chelator TPEN [N,N,N,N,tetrakis (2-pyridylmethyl)ethylenediamine] also induced programmed death in this cell line, indicating the existence of intracellular zinc levels below and above which apoptosis is induced. Zincinduced apoptosis in C6 cells was independent of major signaling pathways (protein kinase C, mitogen activated protein kinase and guanylate cyclase) and protein synthesis, but was increased by facilitating zinc uptake with the ionophore pyrithione. Lanthanum(III)chloride was also able to increase the net zinc uptake, but nevertheless apoptotic features and zinc toxicity were reduced. Remarkably, lanthanum suppressed the zincinduced breakdown of the mitochondrial membrane potential. We conclude that in C6 cells lanthanum acts in two different ways, as a promoter of net zinc uptake and as a suppressor of zincinduced apoptosis.
A Structural Role for Asp83 in the Photoactivation of Rhodopsin
Authors: Breikers Githa , Bovee-Geurts Petra H.M. , DeCaluwé Godelieve L.J. , DeGrip Willem J. 
Published: October 2004

AbstractAsp83 is a highly conserved residue in the second transmembrane domain of visual pigments and many members of other G proteincoupled receptor subfamilies. Upon illumination, the rod visual pigment rhodopsin proceeds through various intermediate states (Batho BSI Lumi Meta I Meta II). Meta II represents the active state of rhodopsin, which binds and activates the G protein transducin. Evidence has been presented that Asp83 participates in the formation of Meta II and undergoes a change in Hbonding. To investigate whether this role of Asp83 requires its protondonating capacity and/or its Hbonding capability, we constructed the mutants D83C and D83N. Both mutants appear to effectively activate transducin, indicating that Asp83 is not essential for signal transduction. Differential effects of the mutations D83C and D83N are observed in the spectral properties and the pH sensitivity of the Meta I Meta II transition. In general, D83C behaves much more like wildtype than D83N. We conclude that the structural role of Asp83 also involves the acidic nature of its carboxyl group. In addition, the participation in Meta II formation of Cys83 in D83C manifests itself as a change in the vibrational properties of the sulfhydryl group, demonstrating that the SH group can be used as a noninvasive probe for local structural changes.
Structure, Function and Clinical Significance of Transferrin Receptors
Authors: Feelders Richard A. , Kuiper-Kramer Ellen P. A. , van Eijk Henk G. 
Published: October 2004

Abstract
Iron plays an essential role in a spectrum of metabolic processes. Cellular iron uptake is facilitated by transferrin receptor (TfR)-mediated endocytosis. In recent years more insight has been obtained in TfR physiology and the regulation of cellular iron homeostasis. The synthesis of TfR and the iron storage protein ferritin is regulated reciprocally at the post-transcriptional level according to the cellular iron status. As a result of externalization of TfR during the endocytic cycle, a soluble form of TfR can be detected in serum. The serum TfR (sTfR) level is closely related to erythroid TfR turnover and the prime determinants of the sTfR concentration are cellular iron demands and erythroid proliferation rate. In the absence of a hyperplastic erythropoiesis the sTfR level is a sensitive parameter of early tissue iron deficiency. The entire spectrum of body iron status can be assessed by measurement of serum ferritin and sTfR levels, with ferritin as marker of tissue iron stores and sTfR as index of tissue iron needs. The sTfR may be a promising tool to detect iron deficiency in inflammatory states and in the anaemia of chronic disease as its concentration is, in contrast to ferritin levels, not influenced by the acute phase response. Determination of sTfR levels may also improve assessment of body iron stores during pregnancy and in neonates. Finally, the sTfR may be a useful parameter to monitor erythropoiesis in various clinical settings, for instance in the prediction of the haematological response to erythropoietin treatment. However, standardization of the sTfR assay, with definition of reference and pathological ranges, is necessary for the definitive introduction of the sTfR as major parameter of iron metabolism.
Cardiac Troponin I and Troponin T: Recent Players in the Field of Myocardial Markers
Authors: Chapelle Jean-Paul 
Published: October 2004

Abstract
The troponin (Tn) complex consists of three subunits referred to as TnT, TnI and TnC. Myocardium contains TnT and TnI isoforms which are not present in skeletal muscles and which can be separated from the muscular isoforms by immunological techniques. Using commercially available immunoassays, clinical laboratories are able to determine cardiac TnT and TnI (cTnT and cTnI) quickly and reliably as classical cardiac markers. After acute myocardial infarction, cTnT and cTnI concentrations start to increase in serum in a rather similar way than CK-MB, but return to normal after longer periods of time (approximately one week). Because of their excellent cardiac specificity, Tn subunits appear ideally suited for the differential diagnosis of myocardial and muscular damage, for example in noncardiac surgery patients, in patients with muscular trauma or with chronic muscular diseases, or after intense physical exercise. cTnT and cTnI may also be used for detecting evidence of minor myocardial damage: therefore they have found new clinical applications, in particular risk stratification in patients with unstable angina. In spite of the possible reexpression of cTnT in human skeletal muscles, and of the lack of standardization of cTnI assays, Tn subunits are not far to meet the criteria of ideal markers for acute myocardial injury. Only an insufficient sensitivity in the first hours following the acute coronary syndroms requiries to maintain an early myocardial marker in the cardiac panel for routine laboratory testing.
Fecal Tumor Necrosis Factor alpha, Eosinophil Cationic Protein and IgE Levels in Infants with Cows Milk Allergy and Gastrointestinal Manifestations
Authors: Kapel Nathalie , Matarazzo Pellegrino , Haouchine Djamel , Abiola Nadine , Guérin Sylvie , Magne Denis , Gobert Jean-Gérard , Dupont Christophe 
Published: October 2004

Abstract
Infants with atopic eczema exhibit a specific fecal protein pattern after oral challenge with cow's milk, characterized by an increase in both eosinophil cationic protein (ECP) and tumor necrosis factor (TNF)α. The aim of our study was to determine the pattern of these proteins in allergic infants with intestinal manifestations. TNFα, ECP and immunoglobulin E (IgE) were measured in stools from 13 infants with intestinal symptoms and 10 healthy infants. The allergic infants underwent two stool collections, one before a cow's milk challenge and the other after the challenge, either at the onset of clinical manifestations (n=6) or 15 days after the challenge if no clinical manifestations occurred (n=7). Baseline TNFα, ECP and IgE levels were low in all infants. The concentration of TNFα increased after the challenge in infants positive to challenge (p<0.05) but not in those negative to challenge. ECP and IgE levels remained low after the challenge in all the allergic infants. These data confirm that fecal TNFα and ECP levels indicate various reaction types of food allergy and that different immunologic disturbances lead to atopic eczema or intestinal symptoms during food allergy. Fecal protein pattern can thus be a useful tool in diagnosing food allergy in infants with intestinal manifestations.
Detection of GB Virus C/Hepatitis G Virus RNA by Reverse-Transcription Polymerase Chain Reaction
Authors: Chang Jinhong , Tao Qimin , Wei Lai , Du Shaocai , Wang Hao , Sun Yan 
Published: October 2004

Abstract
Recently, a novel RNA virus, designated GB virus C or hepatitis G virus (GBV-C/HGV) has been identified which may possibly be associated with human hepatitis. In this study, the nucleotide sequences of the partial nonstructural 5 (NS5) gene of GBV-C/HGV derived from sera of eight Chinese patients were determined. The overall degree of nucleotide conservation and the existence of regional highly conserved sequences make this part of the genome suitable for the development of diagnostic reagents. On the basis of sequence analysis, two sets of oligonucleotide primers were designed to establish a nested polymerase chain reaction (PCR) for detection of GBV-C/HGV RNA. The efficacy of three PCR methods (first, one stage PCR, second, nested PCR with primers from the NS5 region designed according to the prototype sequence and the third, our newly developed PCR) was compared in 133 Chinese patients with liver disease. The positive rates of these three methods were 8.3 %, 11.3 % and 18.0 % respectively. The specificity of our PCR detecting system was verified by sequencing and restriction fragment length polymorphism (RFLP). In conclusion, because of the heterogeneity and geographic distribution character of GBV-C/HGV, it is necessary to assess the sequence variation among Chinese patients infected with GBV-C/HGV. This may allow to identify GBV-C/HGV RNA with high sensitivity and specificity.
Intracellular and Extracellular, Ionized and Total Magnesium in Pre-Eclampsia and Uncomplicated Pregnancy
Authors: Sanders Renata , Konijnenberg Alice , Huijgen Henk J. , Wolf Hans , Boer Kees , Sanders Gerard T. B. 
Published: October 2004

Abstract
Magnesium (Mg) and calcium (CA) concentrations in women with pre-eclampsia, women with an uncomplicated pregnancy and non-pregnant women were compared. Ionized serum magnesium and calcium concentrations and intracellular magnesium concentrations were measured in 15 pregnant women with severe pre-eclampsia, 34 uncomplicated pregnant women early, at midterm and preterm in their pregnancy and 24 non-pregnant women.
The ionized calcium concentration did not chance during normal pregnancy or during pre-eclampsia relative to non-pregnant women. In contrast, elevated total and ionized magnesium serum concentrations were found in women with severe pre-eclampsia (total Mg = 0.85 ± 0.11 mM, ionized Mg = 0.61 ± 0.06 mM) relative to uncomplicated pregnant women (total Mg = 0.72 ± 0.06 mM, ionized Mg = 0.53 ± 0.03 mM). Total magnesium in pre-eclamptic women were similar to non-pregnant women.
Intracellular ionized and total magnesium concentrations in mononuclear blood cells and erythrocytes were similar in pre-eclamptic women and women with uncomplicated pregnancy.
Serum magnesium concentrations are elevated in severe pre-eclamptic women relative to women with uncomplicated pregnancy and are related to birth weight and gestational age at delivery. There may be a causal relationship since magnesium is involved in blood pressure regulation through an intracellular inhibition of NO synthase in endothelial cells.