bluuebunny/crossref_metadata_2025 huggingface dataset:
FULLY RESIDUALLY FREE GROUPS AND GRAPHS LABELED BY INFINITE WORDS
Authors: MYASNIKOV ALEXEI G. , REMESLENNIKOV VLADIMIR N. , SERBIN DENIS E.
Published: September 2006

Let F = F(X) be a free group with basis X and ℤ[t] be a ring of polynomials with integer coefficients in t. In this paper we develop a theory of (ℤ[t],X)-graphs — a powerful tool in studying finitely generated fully residually free (limit) groups. This theory is based on the Kharlampovich–Myasnikov characterization of finitely generated fully residually free groups as subgroups of the Lyndon's group Fℤ[t], the author's representation of elements of Fℤ[t] by infinite (ℤ[t],X)-words, and Stallings folding method for subgroups of free groups. As an application, we solve the membership problem for finitely generated subgroups of Fℤ[t], as well as for finitely generated fully residually free groups.
A GATHERING PROCESS IN ARTIN BRAID GROUPS
Authors: ESYP EVGEINJ S. , KAZACHKOV ILYA V.
Published: September 2006

In this paper we construct a gathering process by the means of which we obtain new normal forms in braid groups. The new normal forms generalize Artin–Markoff normal forms and possess an extremely natural geometric description. In the two last sections of the paper we discuss the implementation of the introduced gathering process and the questions that arose in our work. This discussion leads us to some interesting observations, in particular, we offer a method of generating a random braid.
TEST RANK OF F/R′ LIE ALGEBRAS
Authors: ESMERLIGIL ZERRIN , KAHYALAR DILEK , EKICI NAIME
Published: September 2006

Let F be a free Lie algebra of finite rank n and R be an ideal of F such that the universal enveloping algebra U(F/R) for F/R is an integral domain satisfying the Ore condition. We show that test rank for the Lie algebras of the form F/R′ is equal to n - 1 or n.
REWRITING SYSTEMS IN ALTERNATING KNOT GROUPS
Authors: CHOURAQUI FABIENNE
Published: September 2006

Every tame, prime and alternating knot is equivalent to a tame, prime and alternating knot in regular position, with a common projection. In this work, we show that the augmented Dehn presentation of the knot group of a tame, prime, alternating knot in regular position, with a common projection has a finite and complete rewriting system. This provides an algorithm for solving the word problem with this presentation and we find an algorithm for solving the word problem with the Dehn presentation also.
NON-LIPSCHITZ STOCHASTIC DIFFERENTIAL EQUATIONS DRIVEN BY MULTI-PARAMETER BROWNIAN MOTIONS
Authors: ZHANG XICHENG , ZHU JINGYANG
Published: September 2006

By proving an extension of nonlinear Bihari's inequality (including Gronwall's inequality) to multi-parameter and non-Lebesgue measure, in this paper we first prove by successive approximation the existence and uniqueness of solution of stochastic differential equation with non-Lipschitz coefficients and driven by multi-parameter Brownian motion. Then we study two discretizing schemes for this type of equation, and obtain their L2-convergence speeds.
WinBEST-KIT: WINDOWS-BASED BIOCHEMICAL REACTION SIMULATOR FOR METABOLIC PATHWAYS
Authors: SEKIGUCHI TATSUYA , OKAMOTO MASAHIRO
Published: September 2006

We have implemented an efficient, user-friendly biochemical reaction simulator called Web-based BEST-KIT (Biochemical Engineering System analyzing Tool-KIT) for analyzing large-scale nonlinear networks such as metabolic pathways. Users can easily design and analyze an arbitrary reaction scheme through the Internet and an efficient graphical user interface without considering the mathematical equations. The reaction scheme can include several reaction types, which are represented by both the mass action law (mass balance) and approximated velocity functions of enzyme kinetics at steady state, such as Michaelis-Menten, Hill cooperative, Competitive inhibition. However, since all modules in Web-based BEST-KIT have been developed in Java™ applet style, users cannot optionally make use of original mathematical equations in addition to the prepared equations. In the present study, we have developed a new version of BEST-KIT (for Microsoft® Windows® called WinBEST-KIT) to allow users to define original mathematical equations and to customize these equations very easily as user-defined reaction symbols. The following powerful system-analytical methods are prepared for system analysis: time-course calculation, parameter scanning, estimation of the values of unknown kinetic parameters based on experimentally observed time-course data of reactants, dynamic response of reactants against virtual external perturbations, and real-time simulation (Virtual Dry Lab).
APPLYING ROBUST DIRECTIONAL SIMILARITY BASED CLUSTERING APPROACH RDSC TO CLASSIFICATION OF GENE EXPRESSION DATA
Authors: LI H. X , WANG SHITONG , XIU YU
Published: September 2006

Despite the fact that the classification of gene expression data from a cDNA microarrays has been extensively studied, nowadays a robust clustering method, which can estimate an appropriate number of clusters and be insensitive to its initialization has not yet been developed. In this work, a novel Robust Clustering approach, RDSC, based on the new Directional Similarity measure is presented. This new approach RDSC, which integrates the Directional Similarity based Clustering Algorithm, DSC, with the Agglomerative Hierarchical Clustering Algorithm, AHC, exhibits its robustness to initialization and its capability to determine the appropriate number of clusters reasonably. RDSC has been successfully employed to both artificial and benchmarking gene expression datasets. Our experimental results demonstrate its distinctive superiority over the conventional method Kmeans and the two typical directional clustering algorithms SPKmeans and moVMF.
ANGLE: A SEQUENCING ERRORS RESISTANT PROGRAM FOR PREDICTING PROTEIN CODING REGIONS IN UNFINISHED cDNA
Authors: SHIMIZU KANA , ADACHI JUN , MURAOKA YOICHI
Published: September 2006

In the process of making full-length cDNA, predicting protein coding regions helps both in the preliminary analysis of genes and in any succeeding process. However, unfinished cDNA contains artifacts including many sequencing errors, which hinder the correct evaluation of coding sequences. Especially, predictions of short sequences are difficult because they provide little information for evaluating coding potential. In this paper, we describe ANGLE, a new program for predicting coding sequences in low quality cDNA. To achieve error-tolerant prediction, ANGLE uses a machine-learning approach, which makes better expression of coding sequence maximizing the use of limited information from input sequences. Our method utilizes not only codon usage, but also protein structure information which is difficult to be used for stochastic model-based algorithms, and optimizes limited information from a short segment when deciding coding potential, with the result that predictive accuracy does not depend on the length of an input sequence. The performance of ANGLE is compared with ESTSCAN on four dataset each of them having a different error rate (one frame-shift error or one substitution error per 200–500 nucleotides) and on one dataset which has no error. ANGLE outperforms ESTSCAN by 9.26% in average Matthews's correlation coefficient on short sequence dataset (< 1000 bases). On long sequence dataset, ANGLE achieves comparable performance.
A NOTE ON PHASING LONG GENOMIC REGIONS USING LOCAL HAPLOTYPE PREDICTIONS
Authors: ESKIN ELEAZAR , SHARAN RODED , HALPERIN ERAN
Published: September 2006

The common approaches for haplotype inference from genotype data are targeted toward phasing short genomic regions. Longer regions are often tackled in a heuristic manner, due to the high computational cost. Here, we describe a novel approach for phasing genotypes over long regions, which is based on combining information from local predictions on short, overlapping regions. The phasing is done in a way, which maximizes a natural maximum likelihood criterion. Among other things, this criterion takes into account the physical length between neighboring single nucleotide polymorphisms. The approach is very efficient and is applied to several large scale datasets and is shown to be successful in two recent benchmarking studies (Zaitlen et al., in press; Marchini et al., in preparation). Our method is publicly available via a webserver at .
Calcium controls smooth muscle TRPC gene transcription via the CaMK/calcineurin-dependent pathways
Authors: Morales Sara , Diez Amalia , Puyet Antonio , Camello Pedro J. , Camello-Almaraz Cristina , Bautista Jose M. , Pozo María J.
Published: September 2006

Transient receptor potential protein family C (TRPC) has been proposed as a candidate for channels involved in capacitative Ca2+ entry (CCE) mechanisms, but the modulation of their gene expression remains unexplored. In this study we show that guinea pig gallbladder smooth muscle contains mRNA encoding TRPC1, TRPC2, TRPC3, and TRPC4 proteins whose abundance depends on cytosolic Ca2+ level ([Ca2+]i). Thus lowering the levels of cellular calcium with the chelators EGTA and BAPTA AM results in a downregulation of TRPC1–TRPC4 gene and protein expression. In contrast, activation of Ca2+ influx through L-type Ca2+ channels and Ca2+ release from intracellular stores induced an increase in TRPC1–TRPC4 mRNA and protein abundance. Activation of Ca2+/calmodulin-dependent kinases (CaMK) and phosphorylation of cAMP-response element binding protein accounts for the increase in TRPC mRNA transcription in response to L-type channel-mediated Ca2+ influx . In addition to this mechanism, activation of TRPC gene expression by intracellular Ca2+ release also involves calcineurin pathway. According to the proposed role for these channels, activation of CCE induced an increase in TRPC1 and TRPC3 mRNA abundance, which depends on the integrity of the calcineurin and CaMK pathways. These findings show for the first time an essential autoregulatory role of Ca2+ in Ca2+ homeostasis at the level of TRPC gene and protein expression.
Episodic ataxia type 1 mutation F184C alters Zn2+-induced modulation of the human K+ channel Kv1.4-Kv1.1/Kvβ1.1
Authors: Imbrici Paola , D'Adamo Maria Cristina , Cusimano Antonella , Pessia Mauro
Published: September 2006

Episodic ataxia type 1 (EA1) is a Shaker-like channelopathy characterized by continuous myokymia and attacks of imbalance with jerking movements of the head, arms, and legs. Although altered expression and gating properties of Kv1.1 channels underlie EA1, several disease-causing mechanisms remain poorly understood. It is likely that Kv1.1, Kv1.4, and Kvβ1.1 subunits form heteromeric channels at hippocampal mossy fiber boutons from which Zn2+ ions are released into the synaptic cleft in a Ca2+-dependent fashion. The sensitivity of this macromolecular channel complex to Zn2+ is unknown. Here, we show that this heteromeric channel possesses a high-affinity (<10 μM) and a low-affinity (<0.5 mM) site for Zn2+, which are likely to regulate channel availability at distinct presynaptic membranes. Furthermore, the EA1 mutation F184C, located within the S1 segment of the Kv1.1 subunit, markedly decreased the equilibrium dissociation constants for Zn2+ binding to the high- and low-affinity sites. The functional characterization of the Zn2+ effects on heteromeric channels harboring the F184C mutation also showed that this ion significantly 1) slowed the activation rate of the channel, 2) increased the time to reach peak current amplitude, 3) decreased the rate and amount of current undergoing N-type inactivation, and 4) slowed the repriming of the channel compared with wild-type channels. These results demonstrate that the EA1 mutation F184C will not only sensitize the homomeric Kv1.1 channel to extracellular Zn2+, but it will also endow heteromeric channels with a higher sensitivity to this metal ion. During the vesicular release of Zn2+, its effects will be in addition to the intrinsic gating defects caused by the mutation, which is likely to exacerbate the symptoms by impairing the integration and transmission of signals within specific brain areas.
LPS inhibits fasted plasma ghrelin levels in rats: role of IL-1 and PGs and functional implications
Authors: Wang Lixin , Basa Nicole R. , Shaikh Almaas , Luckey Andrew , Heber David , St-Pierre David H. , Taché Yvette
Published: September 2006

LPS injected intraperitoneally decreases fasted plasma levels of ghrelin at 3 h postinjection in rats. We characterized the inhibitory action of LPS on plasma ghrelin and whether exogenous ghrelin restores LPS-induced suppression of food intake and gastric emptying in fasted rats. Plasma ghrelin and insulin and blood glucose were measured after intraperitoneal injection of LPS, intravenous injection of IL-1β and urocortin 1, and in response to LPS under conditions of blockade of IL-1 or CRF receptors by subcutaneous injection of IL-1 receptor antagonist (IL-1Ra) or astressin B, respectively, and prostaglandin (PG) synthesis by intraperitoneal indomethacin. Food intake and gastric emptying were measured after intravenous injection of ghrelin at 5 h postintraperitoneal LPS injection. LPS inhibited the elevated fasted plasma ghrelin levels by 47.6 ± 4.9%, 58.9 ± 3.3%, 74.4 ± 2.7%, and 48.9 ± 8.7% at 2, 3, 5, and 7 h postinjection, respectively, and values returned to preinjection levels at 24 h. Insulin levels were negatively correlated to those of ghrelin, whereas there was no significant correlation between glucose and ghrelin. IL-1Ra and indomethacin prevented the first 3-h decline in ghrelin levels induced by LPS, whereas astressin B did not. IL-1β inhibited plasma ghrelin levels, whereas urocortin 1 had no influence. Ghrelin injected intravenously prevented an LPS-induced 87% reduction of gastric emptying and 61% reduction of food intake. These data showed that IL-1 and PG pathways are part of the early mechanisms by which LPS suppresses fasted plasma ghrelin and that exogenous ghrelin can normalize LPS-induced-altered digestive functions.
Ethanol Inhibition of M-Current and Ethanol-Induced Direct Excitation of Ventral Tegmental Area Dopamine Neurons
Authors: Koyama Susumu , Brodie Mark S. , Appel Sarah B.
Published: September 2006

Ethanol-induced excitation of ventral tegmental area dopamine (DA VTA) neurons is thought to be critical for the reinforcing effects of ethanol. Although ligand-gated ion channels are known to be the targets of ethanol, ethanol modulation of voltage-dependent ion channels of central neurons has not been well studied. We have demonstrated that ethanol excites DA VTA neurons by the reduction of sustained K+currents and recently reported that M-current ( IM) regulates action potential generation through fast and slow afterhyperpolarization phases. In the present study we thus examined whether ethanol inhibition of IMcontributes to the excitation of DA VTA neurons using nystatin-perforated patch current- and voltage-clamp recordings. Ethanol (20–120 mM) reduced IMin a concentration-dependent manner and increased the spontaneous firing frequency of DA VTA neurons. Ethanol-induced increase in spontaneous firing frequency correlated positively with ethanol inhibition of IMwith a slope value of 1.3. Specific IMinhibition by XE991 (0.3–10 μM) increased spontaneous firing frequency which correlated positively with IMinhibition with a slope value of 0.5. In the presence of 10 μM XE991, a concentration that produced maximal inhibition of IM, ethanol still increased the spontaneous firing frequency of DA VTA neurons in a concentration-dependent manner. Thus we conclude that, although ethanol causes inhibition of IMand this results in some increase in the firing frequency of DA VTA neurons, another effect of ethanol is primarily responsible for the ethanol-induced increase in firing rate in these neurons.
Preparatory Gain Modulation of Visuomotor Transmission for Smooth Pursuit Eye Movements in Monkeys
Authors: Tabata Hiromitsu , Miura Kenichiro , Taki Masakatsu , Matsuura Kiyoto , Kawano Kenji
Published: September 2006

It has been reported that the visuomotor processing underlying the initiation of smooth pursuit eye movement is modulated in relation to the recent experience of eye movements: the initial pursuit eye velocity is larger after experiencing repeated pursuits than saccades. To assess which parameters of the previously executed pursuits play an essential role in modulating the gain of visuomotor transmission, we recorded the ocular responses of monkeys to a brief perturbing motion of the tracking target injected before the start of the eye movements. First, we compared the perturbation responses among the blocks in which the duration of executing pursuit was varied. We found that the response amplitude increased with the increase of the pursuit duration and it reached a plateau level at 100–200 ms of the duration. Second, a comparison of the perturbation responses in the blocks in which target velocity was different showed a gradual increase of the response as a function of the required pursuit velocity. Third, when the animals repeatedly performed pursuits, the response amplitude gradually increased with increasing interval between the appearance of the target and the onset of perturbation. On the other hand, such an increase was not observed when the animals repeatedly performed saccades. These results suggest that before initiating eye movements, the pursuit system modulates the gain of visuomotor transmission so as to be closely related to the properties of the repeatedly experienced eye movements and this gain modulation is triggered by the target’s appearance.
Association of a novel regulatory polymorphism (−938C>A) in the BCL2 gene promoter with disease progression and survival in chronic lymphocytic leukemia
Authors: Nückel Holger , Frey Ulrich H. , Bau Maja , Sellmann Ludger , Stanelle Jens , Dürig Jan , Jöckel Karl-Heinz , Dührsen Ulrich , Siffert Winfried
Published: September 2006

Bcl-2 plays a key role in the regulation of apoptosis. We investigated the role of a novel regulatory single-nucleotide polymorphism (−938C>A) in the inhibitory P2 BCL2 promoter in B-cell chronic lymphocytic leukemia (B-CLL). The −938C allele displayed significantly increased BCL2 promoter activity and binding of nuclear proteins compared with the A allele. Concomitantly, Bcl-2 protein expression in B cells from CLL patients carrying the −938 AA genotype was significantly increased compared with CC genotypes. Genotype distribution between 123 CLL patients (42 AA, 55 AC, 26 CC) and 120 genotyped healthy controls (36 AA, 63 AC, 21 CC) was not significantly different, suggesting that genotypes of this polymorphism do not increase the susceptibility for B-CLL. However, median time from first diagnosis to initiation of chemotherapy and median overall survival were significantly shorter in patients with −938AA genotype (38 and 199 months, respectively) compared with AC/CC genotypes (120 and 321 months, respectively; P = .008 and P = .003, respectively). Multivariable Cox regression identified the BCL2−938AA genotype as an independent prognostic factor for the time to first treatment (hazard ratio [HR] 1.9; P = .034) together with disease stage at diagnosis (HR 2.5; P = .004) and ZAP-70 status (HR 3.0; P = .001). The BCL2−938AA genotype is associated with increased Bcl-2 expression and a novel unfavorable genetic marker in patients with B-CLL.
Genetic analysis of the GRIK2modifier effect in Huntington's disease
Authors: Zeng Wenqi , Gillis Tammy , Hakky Michael , Djoussé Luc , Myers Richard H , MacDonald Marcy E , Gusella James F
Published: September 2006

Background

In Huntington's disease (HD), age at neurological onset is inversely correlated with the length of the CAG trinucleotide repeat mutation, but can be modified by genetic factors beyond the HD gene. Association of a relatively infrequent 16 TAA allele of a trinucleotide repeat polymorphism in the GRIK2 3'UTR with earlier than expected age at neurological onset has been suggested to reflect linkage disequilibrium with a functional polymorphism in GRIK2 or an adjacent gene.

Results

We have tested this hypothesis by sequencing all GRIK2 exons, the exon-flanking sequences and 3'UTR in several individuals who were crucial to demonstrating the modifier effect, as they showed much earlier age at neurological onset than would be expected from the length of their HD CAG mutation. Though ten known SNPs were detected, no sequence variants were found in coding or adjacent sequence that could explain the modifier effect by linkage disequilibrium with the 16 TAA allele. Haplotype analysis using microsatellites, known SNPs and new variants discovered in the 3'UTR argues against a common ancestral origin for the 16 TAA repeat alleles in these individuals.

Conclusion

These data suggest that the modifier effect is actually due to the TAA repeat itself, possibly via a functional consequence on the GRIK2 mRNA.
Magnetic resonance mammography in the evaluation of recurrence at the prior lumpectomy site after conservative surgery and radiotherapy
Authors: Preda Lorenzo , Villa Gaetano , Rizzo Stefania , Bazzi Luca , Origgi Daniela , Cassano Enrico , Bellomi Massimo
Published: September 2006

Introduction

The aim was to assess the value of magnetic resonance mammography (MRM) in the detection of recurrent breast cancer on the prior lumpectomy site in patients with previous conservative surgery and radiotherapy.

Methods

Between April 1999 and July 2003, 93 consecutive patients with breast cancer treated with conservative surgery and radiotherapy underwent MRM, when a malignant lesion on the site of lumpectomy was suspected by ultrasound and/or mammography. MRM scans were evaluated by morphological and dynamic characteristics. MRM diagnosis was compared with histology or with a 36-month imaging follow-up. Enhancing areas independent of the prior lumpectomy site, incidentally detected during the MRM, were also evaluated.

Results

MRM findings were compared with histology in 29 patients and with a 36-month follow-up in 64 patients. MRM showed 90% sensitivity, 91.6% specificity, 56.3% positive predictive value and 98.7% negative predictive value for detection of recurrence on the surgical scar. MRM detected 13 lesions remote from the scar. The overall sensitivity, specificity, positive predictive value and negative predictive value of MRM for detection of breast malignancy were 93.8%, 90%, 62.5% and 98.8%, respectively.

Conclusion

MRM is a sensitive method to differentiate recurrence from post-treatment changes at the prior lumpectomy site after conservative surgery and radiation therapy. The high negative predictive value of this technique can avoid unnecessary biopsies or surgical treatments.
Recognition and Representation of Function Words in English‐Learning Infants
Authors: Shi Rushen , Werker Janet F. , Cutler Anne
Published: September 2006

We examined infants' recognition of functors and the accuracy of the representations that infants construct of the perceived word forms. Auditory stimuli were “Functor + Content Word” versus “Nonsense Functor + Content Word” sequences. Eight‐, 11‐, and 13‐month‐old infants heard both real functors and matched nonsense functors (prosodically analogous to their real counterparts but containing a segmental change). Results reveal that 13‐month‐olds recognized functors with attention to segmental detail. Eight‐month‐olds did not distinguish real versus nonsense functors. The performance of 11‐month‐olds fell in between that of the older and younger groups, consistent with an emerging recognition of real functors. The three age groups exhibited a clear developmental trend. We propose that in the earliest stages of vocabulary acquisition, function elements receive no segmentally detailed representations, but such representations are gradually constructed so that once vocabulary growth starts in earnest, fully specified functor representations are in place to support it.
Integrin traffic
Authors: Pellinen Teijo , Ivaska Johanna
Published: September 2006

Cell adhesion, migration and the maintenance of cell polarity are all processes that depend on the correct targeting of integrins and the dynamic remodelling of integrin-containing adhesion sites. The importance of the endo/exocytic cycle of integrins as a key regulator of these functions is increasingly recognized. Several recent publications have provided mechanistic insight into how integrin traffic is regulated in cells. Increasing evidence suggests that small GTPases such as Arf6 and members of the Rab family control integrin internalization and recycling back to the plasma membrane along microtubules. The fine tuning of these trafficking events seems to be mediated by specific guanine-nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs). In addition, several kinases regulate integrin traffic. The identification of their substrates has demonstrated how these kinases regulate integrin traffic by controlling small GTPases or stabilizing cytoskeletal tracks that are crucial for efficient traffic of integrins to the plasma membrane.
Searching for IRES
Authors: Baird Stephen D. , Turcotte Marcel , Korneluk Robert G. , Holcik Martin
Published: September 2006

The cell has many ways to regulate the production of proteins. One mechanism is through the changes to the machinery of translation initiation. These alterations favor the translation of one subset of mRNAs over another. It was first shown that internal ribosome entry sites (IRESes) within viral RNA genomes allowed the production of viral proteins more efficiently than most of the host proteins. The RNA secondary structure of viral IRESes has sometimes been conserved between viral species even though the primary sequences differ. These structures are important for IRES function, but no similar structure conservation has yet to be shown in cellular IRES. With the advances in mathematical modeling and computational approaches to complex biological problems, is there a way to predict an IRES in a data set of unknown sequences? This review examines what is known about cellular IRES structures, as well as the data sets and tools available to examine this question. We find that the lengths, number of upstream AUGs, and %GC content of 5′-UTRs of the human transcriptome have a similar distribution to those of published IRES-containing UTRs. Although the UTRs containing IRESes are on the average longer, almost half of all 5′-UTRs are long enough to contain an IRES. Examination of the available RNA structure prediction software and RNA motif searching programs indicates that while these programs are useful tools to fine tune the empirically determined RNA secondary structure, the accuracy of de novo secondary structure prediction of large RNA molecules and subsequent identification of new IRES elements by computational approaches, is still not possible.
An accurate fluorescent assay for quantifying the extent of RNA editing
Authors: Roberson Loretta M. , Rosenthal Joshua J.C.
Published: September 2006

Recent data suggest that small differences in editing efficiency can have significant functional consequences. Here we present a fluorescent poisoned primer extension assay that is capable of distinguishing editing efficiency differences as low as 5%. For a poison-primer extension assay to be accurate, the extension product must stop at the intended base. Sometimes, however, it runs beyond. We tested the effect of specific enzyme–terminator combinations on the amount of run through. In the worst cases it accounted for 70% of the total signal, and in the best cases <5%. In addition, the specific base can affect run through, with G producing the least. The accuracy of the assay was demonstrated on templates derived from mixed plasmids and then verified on two biological substrates. Using either a K+ channel mRNA that contains a site for adenosine deamination or an ndhB mRNA that contains a site for cytidine deamination, the editing efficiency predicted by the assay closely matched that predicted by bulk sequencing of individual cDNA clones. This assay should prove useful for analyzing small changes in editing efficiency or for quantifying single nucleotide polymorphisms.
Medial orbital blow‐out fracture: A case report
Authors: Maisel Robert H. , Acomb Thomas E. , Cantrell Robert W.
Published: September 2006

A case report of orbital blow‐out fracture with medial rectus muscle entrapment is described. Over one‐third of the patients with blow‐out fractures of the orbital floor also sustain medial wall injury. Five previous case reports of medial entrapment are reviewed. The mechanism of injury is hydraulic, and the medial muscle incarceration in the fracture may produce an orbital retraction syndrome. Exploratory surgery is recommended through an external orbito‐ethmoid approach.
Subcellular Localization of CIAPIN1
Authors: Hao Zhiming , Li Xiaohua , Qiao Taidong , Du Rui , Zhang Guoyun , Fan Daiming
Published: September 2006

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a newly identified anti-apoptotic molecule. Our previous studies have demonstrated that CIAPIN1 is ubiquitously expressed in normal fetal and adult human tissues and confers multidrug resistance in gastric cancer cells, possibly by upregulating the expression of multidrug resistance gene 1 and multidrug resistance-related protein 1. However, fundamental biological functions of CIAPIN1 have not been elucidated. In this study, we first predicted the subcellular localization of CIAPIN1 with bioinformatic approaches and then characterized the intracellular localization of CIAPIN1 in both human and mouse cells by a combination of techniques including (a) immunohistochemistry and immunofluorescence, (b) His-tagged CIAPIN1 expression, and (c) sub-cellular fractionation and analysis of CIAPIN1 in the fractions by Western blotting. All methods produced consistent results; CIAPIN1 was localized in both the cytoplasm and the nucleus and was accumulated in the nucleolus. Bioinformatic prediction disclosed a putative nuclear localization signal and a putative nuclear export signal within both human and mouse CIAPIN1. These findings suggest that CIAPIN1 may undergo a cytoplasm-nucleus-nucleolus translocation.
Lysosomal Destabilization Contributes to Apoptosis of Germinal Center B-lymphocytes
Authors: van Nierop Kirsten , Muller Femke J.M. , Stap Jan , Van Noorden Cornelis J.F. , van Eijk Marco , de Groot Cornelis
Published: September 2006

During germinal center (GC) reactions, B-lymphocytes with high-affinity B-cell receptors are selected. Regulation of apoptosis is a key process in selecting such wanted B-cells and in eliminating B-cells with unwanted specificities. In this paper, we show that apoptosis in human GC B-cells involves lysosomal destabilization, which is strictly controlled by caspase-8 activity, but not by caspase-9 activity. Ligation of CD40 provides resistance to lysosomal destabilization. Experimental lysosomal rupture by the lysosomotropic drug O-methyl-L-serine dodecylamide hydrochloride (MSDH) induces apoptosis in GC B-cells, including phosphatidyl serine exposure, mitochondrial inactivation, and DNA fragmentation. These apoptotic features occur in the absence of caspase-3 activity. Follicular dendritic cells (FDCs) protect binding B-lymphocytes from lysosomal destabilization, in both the absence and the presence of MSDH. Our study demonstrates that lysosomal leakage induces apoptosis of GC B-cells in a caspase-3-independent manner and that high-affinity binding to FDCs prevents lysosomal leakage and apoptosis in GC B-cells.
Direct Detection of Herceptin/Trastuzumab Binding on Breast Tissue Sections
Authors: Glazyrin Alexey , Shen Xiaoyun , Blanc Victoria , Eliason James F.
Published: September 2006

The protooncogene product HER-2/ neu is the target of the humanized monoclonal antibody trastuzumab (Herceptin). Several tests are used clinically to identify patients with HER-2/ neu overexpression based on evaluation by pathologists of gene amplification by fluorescence in situ hybridization or protein expression using immunohistochemistry (IHC). A simple technique has been developed for staining formalin-fixed, paraffin-embedded breast cancer tissue using unmodified Herceptin/trastuzumab as the primary antibody. Results were compared with staining with the commercial kit, HercepTest, as well as with polyclonal anti-HER-2/ neu antibodies and with biotinylated trastuzumab. These procedures were tested using four breast cancer microarrays. There were 854 cores that were stained with all four antibodies, representing 325 cases. A standard 4-point scoring system (0-3) was used. A total of 156 cases (48%) were scored as 0 by all the methods used and 31 (9.5%) were positive (3+) by all methods. Of interest, three cases scored negative using polyclonal anti-HER-2/ neu antibodies but were positive using unmodified trastuzumab. To clarify this discrepancy, whole sections of tumors were examined with both antibodies using double labeling. There were some tumors that demonstrated a mosaic pattern of staining with neighboring cells or groups of cells stained exclusively with one antibody or the other. These results demonstrate that unmodified humanized or human therapeutic antibodies could be used for preclinical testing or in a clinical laboratory setting for IHC-based selection of patients for treatment, and results of such selection could be different from those obtained using polyclonal antibody-based IHC procedure.
Cellular Localization of PRL-1 and PRL-2 Gene Expression in Normal Adult Human Tissues
Authors: Dumaual Carmen M. , Sandusky George E. , Crowell Pamela L. , Randall Stephen K.
Published: September 2006

Recent evidence suggests that the PRL-1 and −2 phosphatases may be multifunctional enzymes with diverse roles in a variety of tissue and cell types. Northern blotting has previously shown widespread expression of both transcripts; however, little is known about the cell type-specific expression of either gene, especially in human tissues. Therefore, we investigated expression patterns for PRL-1 and −2 genes in multiple normal, adult human tissues using in situ hybridization. Although both transcripts were ubiquitously expressed, they exhibited strikingly different patterns of expression. PRL-2 was expressed heavily in almost every tissue and cell type examined, whereas PRL-1 expression levels varied considerably both between tissue types and between individuals. Widespread expression of PRL-1 and −2 in multiple organ systems suggests an important functional role for these enzymes in normal tissue homeostasis. In addition, the variable patterns of expression for these genes may provide distinct activities in each tissue or cell type.
Verbal Memory and IQ in Children who Undergo Focal Resection for Intractable Epilepsy:A Clinical Review
Authors: Lah Suncica Sunny , Joy Pamela , Bakker Kathleen , Miller Laurie
Published: September 2006

Previous studies have indicated an increased likelihood of intellectual and memory impairments in children with epilepsy. It has been argued that early surgical intervention in children with intractable seizures might be advantageous to their development. We conducted a retrospective review of pre- and postoperative IQ and verbal memory scores in 16 paediatric patients who underwent temporal (N= 10) or extra-temporal (N= 6) focal surgery for epilepsy. Patients with an extratemporal seizure focus performed significantly worse than patients with a temporal lobe seizure focus on Full Scale IQ and Verbal IQ before surgery. Postoperatively a statistically significant decline in verbal memory, but not in any of the IQ indices was noticed in the extratemporal group. Individual outcome analyses revealed a significant decline in verbal memory in 22% of temporal lobectomy and 60% of extratemporal cases. Our review suggests that verbal memory but not IQ is vulnerable to postoperative decline in children who undergo focal extratemporal surgery for intractable epilepsy. The findings raise the possibility that extratemporal regions play a role in anterograde memory in children. Given the small number of subjects in this study, further investigations into the cognitive effects of paediatric surgical intervention are recommended.
Neuropsychological Outcomes of Children Treated for Posterior Fossa Tumours:A Review
Authors: Stargatt Robyn , Anderson Vicki , Rosenfeld Jeffrey V.
Published: September 2006

The posterior fossa region of the brain is a frequent site for tumour development in children, with over half of all childhood tumours occurring at this site. The principal brain structure implicated at this site is the cerebellum. Children treated for posterior fossa tumours can have a wide range of neurological and psychosocial problems. This paper describes the literature to date that addresses the neuropsychological impact of tumour and treatment in children with posterior fossa tumours. This paper reviews the literature on the causes of morbidity in this group. It discusses the recent research on the role of the cerebellum in outcomes and the studies that identify variables that interact with radiation effects.
Sino-Japanese Rivalry and Its Implications for Developing Nations
Authors: Dreyer June Teufel
Published: September 2006

The PRC's larger size, rapid economic development, and greater international assertiveness would seem to give China a clear edge over Japan. Yet, Beijing's frequently heavy-handed diplomacy and steadily rising defense budgets concern many of its neighbors. While most states are publicly deferential to the PRC's wishes, they have quietly taken steps to accommodate Japan as well.
Taiwan's Participation in Inter-Governmental Organizations: An Overview of Its Initiatives
Authors: Li Chien-pin
Published: September 2006

Emboldened by the ascendance of economic issues on the global agenda and the erosion of security-driven bipolar structures, Taiwan in the late 1980s decided to use its economic advantages for diplomatic gain. Examination of changes in three phases of Taiwan's initiatives indicates that its inter-governmental organization strategies and targets correlate well with domestic politics and external factors.
Regulation of an Unexploited Brown Trout Population in Spruce Creek, Pennsylvania
Authors: Carline Robert F.
Published: September 2006

The purpose of this paper is to describe the annual variations in the density of an unexploited population of lotic brown troutSalmo truttathat has been censused annually for 19 years and to explore the importance of density‐independent and density‐dependent processes in regulating population size. Brown trout density and indices of stream discharge and water temperature were related to annual variations in natural mortality, recruitment, and growth. Annual mortality of age‐1 and older (age‐1+) brown trout ranged from 0.30 to 0.75 and was best explained by discharge during spring and by brown trout density. Recruitment to age 1 varied fivefold. Density of age‐1 brown trout was inversely related to spawner density and positively related to discharge during the fall spawning period. The median length of age‐1 brown trout was positively related to discharge during summer and fall. Relative weight was inversely related to the density of age‐2+ brown trout. The interactive effects of discharge and brown trout density accounted for most of the annual variation in mortality, recruitment, and growth during the first year of life. Annual trends in the abundance of age‐1+ brown trout were largely dictated by natural mortality.
A Mutation in RYK is a Genetic Factor for Nonsyndromic Cleft Lip and Palate
Authors: Watanabe Akira , Akita Sadanori , Tin Nguyen Thi Duc , Natsume Nagato , Nakano Yoko , Niikawa Norio , Uchiyama Takeshi , Yoshiura Koh-ichiro
Published: September 2006

Objective

The RYK, EPHB2, and EPHB3 genes are attractive candidates for cleft lip and/or palate and cleft palate only pathogenesis. Both the Ryk-deficient mouse and Ephb2/Ephb3 (genes for interaction molecules with RYK) double-mutant mouse show cleft palate.

Setting

Mutation searches for RYK, EPHB2, and EPHB3 were carried out in a large number of Japanese and Vietnamese patients with cleft lip and/or palate and cleft palate only. Case-control study and transmission disequilibrium tests were performed also, using three single nucleotide polymorphisms within a linkage disequilibrium block in RYK. Seven haplotypes were constructed from the single nucleotide polymorphisms.

Results

A missense mutation, 1355G>A (Y452C), in RYK was identified in one Vietnamese patient with cleft lip and/or palate. This mutation was not found among 1646 Vietnamese, Japanese, and Caucasians, including 354 cleft lip and/ or palate and cleft palate only patients. Colony formation assay using NIH3T3 cells transfected with mutant cDNA revealed that mutant RYK had significantly reduced protein activity, compared with those with wild-type RYK, implying that the transformation ability of RYK is depleted by this mutation. Although a case-control study and transmission disequilibrium tests on three individual single nucleotide polymorphisms provided no evidence for association with oral clefts, a case-control study on one rare haplotype suggested a positive association in Japanese patients with cleft lip and/or palate and cleft palate only. No mutations in EPHB2 and EPHB3 were found in any patients examined.

Conclusion

The findings suggested that a missense mutation, 1355G>A, and one rare single nucleotide polymorphisms haplotype may play a role in the development of cleft lip and/or palate in the Vietnamese, and cleft lip and/ or palate and cleft palate only in the Japanese.
Audiological Issues in Children with Cleft Lip and Palate in One Area of the U.K.
Authors: Moss A. L. H. , Fonseca S.
Published: September 2006

Objective

The purpose of this study was to determine the extent of multidisciplinary care and audiological services rendered to children with CL/P who underwent surgical repair of the cleft in 1998 and 1999. This followed proposals to radically reorganize cleft lip and palate services in the U.K. after unsatisfactory findings in a national review.

Method

Information was obtained from questionnaires sent to clinicians (audiologists; ear, nose, and throat surgeons; and community pediatricians) from audiology teams, and parents were asked to retrieve information from their Personal Child Health Record. Standards chosen were based on the Clinical Standards Advisory Group, the South Thames Audiology Audit Group, and the National Deaf Children's Society.

Results

None of the agreed standards were achieved at an acceptable level.

Conclusions

This demonstrates the need for better communication systems between teams, including better use by parents and professionals of the Personal Child Health Record. A clinical care pathway is suggested here with other recommendations.
Velopharyngeal Anatomy in 22q11.2 Deletion Syndrome: A Three-Dimensional Cephalometric Analysis
Authors: Ruotolo Rachel A. , Veitia Nestor A. , Corbin Aaron , McDonough Joseph , Solot Cynthia B. , McDonald-McGinn Donna , Zackai Elaine H. , Emanuel Beverly S. , Cnaan Avital , LaRossa Don , Arens Raanan , Kirschner Richard E.
Published: September 2006

Objective

22q11.2 deletion syndrome is the most common genetic cause of velopharyngeal dysfunction (VPD). Magnetic resonance imaging (MRI) is a promising method for noninvasive, three-dimensional (3D) assessment of velopharyngeal (VP) anatomy. The purpose of this study was to assess VP structure in patients with 22q11.2 deletion syndrome by using 3D MRI analysis.

Design

This was a retrospective analysis of magnetic resonance images obtained in patients with VPD associated with a 22q11.2 deletion compared with a normal control group.

Setting

This study was conducted at The Children's Hospital of Philadelphia, a pediatric tertiary care center.

Patients, Participants

The study group consisted of 5 children between the ages of 2.9 and 7.9 years, with 22q11.2 deletion syndrome confirmed by fluorescence in situ hybridization analysis. All had VPD confirmed by nasendoscopy or videofluoroscopy. The control population consisted of 123 unaffected patients who underwent MRI for reasons other than VP assessment.

Interventions

Axial and sagittal T1- and T2-weighted magnetic resonance images with 3-mm slice thickness were obtained from the orbit to the larynx in all patients by using a 1.5T Siemens Visions system.

Outcome Measures

Linear, angular, and volumetric measurements of VP structures were obtained from the magnetic resonance images with VIDA image-processing software.

Results

The study group demonstrated greater anterior and posterior cranial base and atlanto-dental angles. They also demonstrated greater pharyngeal cavity volume and width and lesser tonsillar and adenoid volumes.

Conclusion

Patients with a 22q11.2 deletion demonstrate significant alterations in VP anatomy that may contribute to VPD.
Hard Palate Repair Timing and Facial Morphology in Unilateral Cleft Lip and Palate: before versus after Pubertal Peak Velocity Age
Authors: Liao Yu-Fang , Mars Michael
Published: September 2006

Objective

To investigate whether timing of hard palate repair, before versus after pubertal peak velocity age, had a significant effect on facial growth in patients with unilateral cleft lip and palate.

Design

Retrospective cross-sectional study.

Setting

Sri Lankan Cleft Lip and Palate Project.

Patients

A total of 125 adult patients with nonsyndromic unilateral cleft lip and palate were recruited and their last cephalometric radiographs were used.

Main Outcome Measures

Clinical notes were used to record surgical treatment histories. Cephalometry was used to determine facial morphology.

Results

The patients who had hard palate repair after pubertal peak velocity age had a deeper bony pharynx (Ba-PMP), a longer alveolar maxilla (PMP-A), a longer effective length of the maxilla (Ar-ANS, Ar-A), and as a result had a more favorable anteroposterior jaw relation (ANS-N-Pog, ANB, NAPog) and larger overjet, compared with those who had hard palate repair before pubertal peak velocity age.

Conclusion

Timing of hard palate repair significantly affects the growth of the maxilla in patients with unilateral cleft lip and palate. Hard palate repair after (versus before) pubertal peak velocity age has a smaller adverse effect on the forward growth of the maxilla. This timing affects the forward displacement of the basal maxilla and the anteroposterior development of the maxillary dentoalveolus.
Centralization of Services: Standard Setting and Outcomes
Authors: Hathorn I. S. , Atack N. E. , Butcher G. , Dickson J. , Durning P. , Hammond M. , Knight H. , Mitchell N. , Nixon F. , Shinn D. , Sandy J. R.
Published: September 2006

Objective

To test specific standards set in the newly established cleft lip and palate service in three regions of the U.K. The standards relate to record collection and outcomes.

Design

Retrospective analysis.

Patients

Records of 31 children, 5 years of age, who were born in 1997 with complete unilateral clefts of lip and palate and were treated by surgeons in three regions.

Main outcome measures

Record collection standards were measured by collecting dental study models. Outcomes were measured with the 5-Year-Old Index.

Results

Of the 31 subjects, 52% had excellent and good outcomes. The 31 cases represented 62% of the total records collected.

Conclusions

The three regions examined fell short of the standards set, but the outcomes were improved compared with previous national outcomes. The failings in record collection need to be rectified. This study provides baseline data for further development of cleft services within three regions.
Congenital Fenestration of the Palate: A Case of Embryologic Syzygy
Authors: Rogers Gary F. , Murthy Ananth , Mulliken John B.
Published: September 2006

Congenital fenestration of the secondary palate is the rarest type of facial cleft. Of the 26 putative cases in the literature, only 5 had confirmation of the cleft during the neonatal period. This report documents such a cleft in an infant and presents the likely pathogenesis.