bluuebunny/crossref_metadata_2025 huggingface dataset:
ELECTRONIC TRANSPORT PROPERTIES IN THE SEMICONDUCTOR ALLOY (GaP)0.95(ZnSe)0.05
Authors: Glicksman M. , Gutman D. , Yim W. M.
Published: February 2004

The first measurements of electron transport in n-type alloys of GaP with 5% ZnSe show evidence for strong ionized impurity scattering at room temperature in the temperature dependence of the mobility. However, this scattering requires only about 10% of the Zn and Se atoms to be charged centers, and thus suggests that most of the ZnSe present contributes weakly (perhaps as dipole centers) to the scattering. Hall mobilities of 0.23 cm2/V sec at 77°K and 6.2 cm2/V sec at 300°K were measured.
Flow cytometric sorting of frozen - thawed spermatozoa in sheep and non-human primates
Authors: O'Brien J. K. , Hollinshead F. K. , Evans K. M. , Evans G. , Maxwell W. M. C.
Published: February 2004

Research was conducted in sheep to determine an effective preparation method for high-purity sorting of frozen–thawed spermatozoa. The efficacy of sorting frozen–thawed spermatozoa was then investigated in several non-human primate species. An aliquot of each ejaculate (three rams, three ejaculates per ram) was processed as a fresh control (FRESH). Frozen spermatozoa were thawed and prepared for sorting by no further processing (FT-NEAT), washing (FT-WASH) or gradient centrifugation (FT-GRADIENT) and evaluated for motility at 1 h post-staining and motility and acrosomal status at 0 and 4 h post-sorting. Samples were analysed using a high-speed cell sorter. High levels of purity for X- and Y-enriched samples were achieved for all treatments (85–92%). The percentage of motile spermatozoa before sorting was lower (P < 0.05) for frozen–thawed samples (FT-NEAT: 32.7 ± 2.5%; FT-WASH: 32.2 ± 3.3%; FT-GRADIENT: 73.9 ± 3.7%) compared with FRESH (83.3 ± 1.2%). Post-sorting, the percentage of motile spermatozoa before and after incubation for FT-NEAT (60.0 ± 5.1% and 27.2 ± 6.1% for 0 and 4 h, respectively) was lower than that for FRESH (87.8 ± 0.9% and 83.3 ± 1.2% for 0 and 4 h, respectively; P < 0.05), FT-WASH (80.0 ± 2.4% and 71.7 ± 3.6% for 0 and 4 h, respectively; P < 0.05) and FT-GRADIENT (84.4 ± 1.3% and 77.2 ± 1.7% for 0 and 4 h, respectively; P < 0.05). Vanguard sperm migration distance through artificial cervical mucus was lower (P < 0.05) for FT-NEAT (17.7 ± 1.7 mm) compared with FT-WASH (29.1 ± 3.8 mm) and FT-GRADIENT (28.4 ± 2.0 mm) and similar (P < 0.05) to FRESH (23.7 ± 1.8 mm). Sample preparation using a modified wash method enabled high-purity sorting (range 86–97% purity) of frozen–thawed epididymal spermatozoa in the baboon (Papio hamadryas), common marmoset (Callithrix jacchus) and common chimpanzee (Pan troglodytes). For all non-human primate species, sorted spermatozoa were progressively motile (marmoset: 20.5 ± 5.5%; baboon: 37.5 ± 2.5%; chimpanzee: 73.0 ± 2.0%), acrosome intact (marmoset: 68.5 ± 7.5%; baboon: 89.5 ± 1.5%; chimpanzee: 84.0 ± 1.0%) and able to penetrate an artificial cervical mucus. In summary, high-purity sorting of frozen–thawed ram and non-human primate spermatozoa with recovery of progressively motile, acrosome-intact spermatozoa was possible after processing to remove cryodiluent.
Stem cell-mediated muscle regeneration is enhanced by local isoform of insulin-like growth factor 1
Authors: Musarò Antonio , Giacinti Cristina , Borsellino Giovanna , Dobrowolny Gabriella , Pelosi Laura , Cairns Linda , Ottolenghi Sergio , Cossu Giulio , Bernardi Giorgio , Battistini Luca , Molinaro Mario , Rosenthal Nadia
Published: February 2004

We investigated the mechanism whereby expression of a transgene encoding a locally acting isoform of insulin-like growth factor 1 (mIGF-1) enhances repair of skeletal muscle damage. Increased recruitment of proliferating bone marrow cells to injured
MLC
/
mIgf-1
transgenic muscles was accompanied by elevated bone marrow stem cell production in response to distal trauma. Regenerating
MLC
/
mIgf-1
transgenic muscles contained increased cell populations expressing stem cell markers, exhibited accelerated myogenic differentiation, expressed markers of regeneration and readily converted cocultured bone marrow to muscle. These data implicate mIGF-1 as a powerful enhancer of the regeneration response, mediating the recruitment of bone marrow cells to sites of tissue damage and augmenting local repair mechanisms.
Persistently active cannabinoid receptors mute a subpopulation of hippocampal interneurons
Authors: Losonczy Attila , Biró Ágota A. , Nusser Zoltan
Published: February 2004

Cortical information processing requires an orchestrated interaction between a large number of pyramidal cells and albeit fewer, but highly diverse GABAergic interneurons (INs). The diversity of INs is thought to reflect functional and structural specializations evolved to control distinct network operations. Consequently, specific cortical functions may be selectively modified by altering the input-output relationship of unique IN populations. Here, we report that persistently active cannabinoid receptors, the site of action of endocannabinoids, and the psychostimulants marijuana and hashish, switch off the output (mute) of a unique class of hippocampal INs. In paired recordings between cholecystokinin-immunopositive, mossy fiber-associated INs, and their target CA3 pyramidal cells, no postsynaptic currents could be evoked with single presynaptic action potentials or with repetitive stimulations at frequencies <25 Hz. Cannabinoid receptor antagonists converted these “mute” synapses into high-fidelity ones. The selective muting of specific GABAergic INs, achieved by persistent presynaptic cannabinoid receptor activation, provides a state-dependent switch in cortical networks.
Induction of aneuploidy by increasing chromosomal instability during dedifferentiation of hepatocellular carcinoma
Authors: Wilkens Ludwig , Flemming Peer , Gebel Michael , Bleck Joerg , Terkamp Christof , Wingen Luzie , Kreipe Hans , Schlegelberger Brigitte
Published: February 2004

To gain more insight into the role of chromosomal instability (CIN), the cytogenetic hallmark of most solid tumors, we performed fluorescencein situhybridization (FISH) on interphase nuclei of cytological specimens enabling the correct detection of chromosome copies in intact tumor cells of 18 well (G1), moderately (G2), or poorly (G3) differentiated hepatocellular carcinomas (HCCs). A close correlation between the morphological dedifferentiation and increasing copy numbers and variation of FISH signals was seen for chromosomes 1 and 8, respectively (P≤ 0.0002). Four HCC G1 had constant chromosome patterns for chromosomes 1 and/or 8 with a mean of signals per nucleus ≤5.08 and ≤3 different signal combinations, indicating a low level of CIN, as confirmed by FISH using probes for centromeres of chromosomes 3, 7, and 17. In contrast to this, five HCC G2–3 revealed ≥8.46 signals per nucleus and 23–41 different signal combinations, indicating high levels of CIN. In the remaining cases, signal counts from 5.96–8.46 and 7–15 combinations were seen. Here, nuclei with constant aberration patterns and low copy numbers occurred alongside nuclei with inconstant patterns and high copy numbers. It is evident that in these cases a transition from well to moderately differentiated HCC developed in parallel to an increase in CIN, possibly induced by a major dysregulation of mitotic control mechanisms. In conclusion, CIN may induce a stepwise increase of aneuploidy in HCC that is mirrored by the morphological dedifferentiation of tumor cells.
Correct tonotopic representation is necessary for complex pitch perception
Authors: Oxenham Andrew J. , Bernstein Joshua G. W. , Penagos Hector
Published: February 2004

The ability to extract a pitch from complex harmonic sounds, such as human speech, animal vocalizations, and musical instruments, is a fundamental attribute of hearing. Some theories of pitch rely on the frequency-to-place mapping, or tonotopy, in the inner ear (cochlea), but most current models are based solely on the relative timing of spikes in the auditory nerve. So far, it has proved to be difficult to distinguish between these two possible representations, primarily because temporal and place information usually covary in the cochlea. In this study, “transposed stimuli” were used to dissociate temporal from place information. By presenting the temporal information of low-frequency sinusoids to locations in the cochlea tuned to high frequencies, we found that human subjects displayed poor pitch perception for single tones. More importantly, none of the subjects was able to extract the fundamental frequency from multiple low-frequency harmonics presented to high-frequency regions of the cochlea. The experiments demonstrate that tonotopic representation is crucial to complex pitch perception and provide a new tool in the search for the neural basis of pitch.
An analysis of the gene expression program of mammalian neural progenitor cells
Authors: Livesey F. J. , Young T. L. , Cepko C. L.
Published: February 2004

A diverse range of neural cell types is generated from a pool of dividing stem and progenitor cells in an orderly manner during development. Little is known of the molecular and cellular biology underpinning the intrinsic control of this process. We have used a nonbiased method to purify populations of neural progenitor cells from the murine CNS to characterize the gene expression program of mammalian retinal progenitor cells. Analysis of these data led to the identification of a core set of >800 transcripts enriched in retinal progenitor cells compared to both their immediate postmitotic progeny and to differentiated neurons. This core set was found to be shared by progenitors in other regions of the developing CNS, with important regional differences in key functional families. In addition to providing an expression fingerprint of this cell type, this set highlights several key aspects of progenitor biology.
Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory
Authors: Pascale Alessia , Gusev Pavel A. , Amadio Marialaura , Dottorini Tania , Govoni Stefano , Alkon Daniel L. , Quattrone Alessandro
Published: February 2004

Neuronal ELAV-like proteins (HuB, HuC, and HuD) are highly conserved RNA-binding proteins able to selectively associate with the 3′ UTR of a subset of target mRNAs and increase their cytoplasmic stability and rate of translation. We previously demonstrated the involvement of these proteins in learning, reporting that they undergo a sustained up-regulation in the hippocampus of mice trained in a spatial discrimination task. Here, we extend this finding, showing that a similar up-regulation occurs in the hippocampus of rats trained in another spatial learning paradigm, the Morris water maze. HuD, a strictly neuron-specific ELAV-like protein, is shown to increase after learning, with a preferential binding to the cytoskeletal fraction. HuD up-regulation is associated with an enhancement of GAP-43 mRNA and protein levels, with an apparently increased HuD colocalization with the GAP-43 mRNA and an increased association of neuronal ELAV-like proteins with the GAP-43 mRNA. These learning-dependent biochemical events appear to be spatiotemporally controlled, because they do not occur in another brain region involved in learning, the retrosplenial cortex, and at the level of protein expression they show extinction 1 month after training despite memory retention. By contrast, HuD mRNA levels still remain increased after 1 month in the CA1 region. This persistence may have implications for long-term memory recall.
Antibody to DNA detects scrapie but not normal prion protein
Authors: Zou Wen-Quan , Zheng Jian , Gray Donald M. , Gambetti Pierluigi , Chen Shu G.
Published: February 2004

Prion diseases, a group of fatal neurodegenerative disorders, are characterized by the presence of the abnormal scrapie isoform of prion protein (PrP
Sc
) in affected brains. A conformational change is believed to convert the normal cellular prion protein into PrP
Sc
. Detection of PrP
Sc
for diagnosis and prophylaxis is impaired because available Abs recognizing epitopes on PrP fail to distinguish between PrP
Sc
and normal cellular prion protein. Here, we report that an anti-DNA Ab, OCD4, as well as gene 5 protein, a well established DNA-binding protein, capture PrP from brains affected by prion diseases in both humans and animals but not from unaffected controls. OCD4 appears to immunoreact with DNA (or a DNA-associated molecule) that forms a conformation-dependent complex with PrP in prion diseases. Whereas PrP immunocaptured by OCD4 is largely protease-resistant, a fraction of it remains protease-sensitive. Moreover, OCD4 detects disease-associated PrP >10 times more efficiently than a widely used Ab to PrP. Our finding that anti-DNA Abs and gene 5 protein specifically target disease-associated DNA–PrP complexes in a wide variety of species and disease phenotypes opens new avenues in the study and diagnosis of prion diseases.
Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity
Authors: Preger Ella , Ziv Inbal , Shabtay Ariel , Sher Ifat , Tsang Michael , Dawid Igor B. , Altuvia Yael , Ron Dina
Published: February 2004

Receptor tyrosine kinases (RTKs) control a multitude of biological processes and are therefore subjected to multiple levels of regulation. Negative feedback is one of the mechanisms that provide an effective means to control RTK-mediated signaling. Sef has recently been identified as a specific antagonist of fibroblast growth factor (FGF) signaling in zebrafish and subsequently in mouse and human. Sef encodes a putative type I transmembrane protein that antagonizes the Ras/mitogen-activated protein kinase pathway in all three species. Mouse Sef was also shown to inhibit the phosphatidylinositol 3-kinase pathway. We show here that an alternative splicing mechanism generates an isoform of human Sef, hSef-b, which unlike the previously reported Sef (hSef-a) is a cytosolic protein. Contrary to hSef-a, which is ubiquitously expressed, hSef-b transcripts display a restricted pattern of expression in human tissues. hSef-b inhibits FGF-induced cell proliferation and prevents the activation of mitogen-activated protein kinase without affecting the upstream component MAPK kinase. Furthermore, hSef-b does not antagonize FGF induction of the phosphatidylinositol 3-kinase pathway. In addition to the effects on FGF signaling, hSef-b inhibited cellular response to platelet-derived growth factor but not other RTK ligands. Therefore, alternative splicing of the hSef gene expands the Sef feedback inhibition repertoire of RTK signaling.
Cooperation of the ErbB2 receptor and transforming growth factor β in induction of migration and invasion in mammary epithelial cells
Authors: Seton-Rogers Sarah E. , Lu Yu , Hines Lisa M. , Koundinya Malvika , LaBaer Joshua , Muthuswamy Senthil K. , Brugge Joan S.
Published: February 2004

MCF10A mammary epithelial cells form growth-arrested structures when cultured in three-dimensional basement membrane gels. Activation of the receptor tyrosine kinase ErbB2 induces formation of proliferative structures that share properties with noninvasive early stage lesions. We conducted a genetic screen to identify cDNAs that can cooperate with ErbB2 to induce migration in these cells, with the hypothesis that they would represent candidate “second hits” in the development of invasive breast carcinomas. We found that expression of transforming growth factor (TGF)β1 and TGFβ3 in cells expressing activated ErbB2 induces migration in transwell chambers and invasive behavior in both basement membrane cultures and invasion chambers. The ability of ErbB2 to cooperate with TGFβ correlated with sustained, elevated activation of extracellular signal-regulated kinase (Erk)-mitogen-activated protein kinase. Pharmacological reduction of Erk activity inhibited the cooperative effect of TGFβ and ErbB2 on migration and expression of activated Erk kinase was sufficient to cooperate with TGFβ to induce migration and invasion, suggesting that sustained Erk activation is critical for ErbB2/TGFβ cooperation. In addition, we show that costimulation of ErbB2 and TGFβ induces autocrine secretion of factors that are sufficient to induce migration, but not invasion, by means of both epidermal growth factor receptor-dependent and -independent processes. These results support the role of TGFβ as a pro-invasion factor in the progression of breast cancers with activated ErbB2 and suggest that activation of the Erk and epidermal growth factor receptor pathways are key in mediating these events.
Differentiation and developmental pathways of uropathogenicEscherichia coliin urinary tract pathogenesis
Authors: Justice Sheryl S. , Hung Chia , Theriot Julie A. , Fletcher Daniel A. , Anderson Gregory G. , Footer Matthew J. , Hultgren Scott J.
Published: February 2004

UropathogenicEscherichia coli(UPEC) are capable of forming complex intracellular bacterial communities (IBC) within the superficial umbrella cells of the bladders of C3H and BALB/c mice. By using time-lapse fluorescence videomicroscopy to observe infected mouse bladder explants, we discovered that IBCs formed by uropathogenicE. coliprogressed through four distinct developmental stages that differed with respect to growth rate, bacterial length, colony organization, motility, and its eventual dispersal. In the first phase, bacteria in the IBC were nonmotile, rod shaped, and grew rapidly in loosely organized colonies free in the cytoplasm of the bladder superficial umbrella cells. In the second phase, the loose collection of bacteria in the IBC matured into a slower growing, highly organized biofilm-like community consisting of coccoid bacteria that ultimately filled most of the cytoplasm. In the third phase, bacteria in the biofilm-like state in the IBC switched to a motile rod-shaped phenotype allowing detachment from the community and eventual fluxing out of the host cell. During the fourth phase, the bacteria filamented. Filamentation appeared to be in response to a Toll-like receptor 4-mediated innate defense mechanism. Bacteria that fluxed out of the superficial umbrella cells were able to reenter the IBC developmental cascade but with slower kinetics and ultimately a quiescent reservoir was established. Intracellular growth and filamentation provided an advantage to the bacteria in evading infiltrating polymorphonuclear leukocytes. This work has developed a technique to observe live infected organs and revealed a complex differentiation pathway that facilitates bacterial persistence in the urinary tract.
DNA A-tract bending in three dimensions: Solving the dA
4
T
4
vs. dT
4
A
4
conundrum
Authors: Stefl Richard , Wu Haihong , Ravindranathan Sapna , Sklenář Vladimír , Feigon Juli
Published: February 2004

DNA A-tracts have been defined as four or more consecutive A·T base pairs without a TpA step. When inserted in phase with the DNA helical repeat, bending is manifested macroscopically as anomalous migration on polyacrylamide gels, first observed >20 years ago. An unsolved conundrum is why DNA containing in-phase A-tract repeats of A
4
T
4
are bent, whereas T
4
A
4
is straight. We have determined the solution structures of the DNA duplexes formed by d(GCAAAATTTTGC) [A4T4] and d(CGTTTTAAAACG) [T4A4] with

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counterions by using NMR spectroscopy, including refinement with residual dipolar couplings. Analysis of the structures shows that the ApT step has a large negative roll, resulting in a local bend toward the minor groove, whereas the TpA step has a positive roll and locally bends toward the major groove. For A4T4, this bend is nearly in phase with bends at the two A-tract junctions, resulting in an overall bend toward the minor groove of the A-tract, whereas for T4A4, the bends oppose each other, resulting in a relatively straight helix. NMR-based structural modeling of d(CAAAATTTTG)
15
and d(GTTTTAAAAC)
15
reveals that the former forms a left-handed superhelix with a diameter of ≈110 Å and pitch of 80 Å, similar to DNA in the nucleosome, whereas the latter has a gentle writhe with a pitch of >250 Å and diameter of ≈50 Å. Results of gel electrophoretic mobility studies are consistent with the higher-order structure of the DNA and furthermore depend on the nature of the monovalent cation present in the running buffer.
Methionine sulfoxide reductase A protects neuronal cells against brief hypoxia/reoxygenation
Authors: Yermolaieva Olena , Xu Rong , Schinstock Carrie , Brot Nathan , Weissbach Herbert , Heinemann Stefan H. , Hoshi Toshinori
Published: February 2004

Hypoxia/reoxygenation induces cellular injury by promoting oxidative stress. Reversible oxidation of methionine in proteins involving the enzyme peptide methionine sulfoxide reductase type A (MSRA) is postulated to serve a general antioxidant role. Therefore, we examined whether overexpression of MSRA protected cells from hypoxia/reoxygenation injury. Brief hypoxia increased the intracellular reactive oxygen species (ROS) level in PC12 cells and promoted apoptotic cell death. Adenovirus-mediated overexpression of MSRA significantly diminished the hypoxia-induced increase in ROS and facilitated cell survival. Measurements of the membrane potentials of intact mitochondria in PC12 cells and of isolated rat liver mitochondria showed that hypoxia induced depolarization of the mitochondrial membrane. The results demonstrate that MSRA plays a protective role against hypoxia/reoxygenation-induced cell injury and suggest the therapeutic potential of MSRA in ischemic heart and brain disease.
A Motif Co-Occurrence Approach for Genome-Wide Prediction of Transcription-Factor-Binding Sites inEscherichia coli
Authors: Bulyk Martha L. , McGuire Abigail M. , Masuda Nobuhisa , Church George M.
Published: February 2004

Various computational approaches have been developed for predictingcis-regulatory DNA elements in prokaryotic genomes. We describe a novel method for predicting transcription-factor-binding sites inEscherichia coli. Our method takes advantage of the principle that transcription factors frequently coregulate gene expression, but without requiring prior knowledge of which groups of genes are coregulated. Using position weight matrices for 49 known transcription factors, we examined spacings between pairs of matrix hits. These pairs were assigned probabilities according to the overrepresentation of their separation distance. The functions of many open reading frames (ORFs) downstream from predicted binding sites are unknown, and may correspond to novel regulon members. For five predictions, knockouts with mutated replacements of the predicted binding sites were created inE. coliMG1655. Quantitative real-time PCR (RT-PCR) indicates that for each of the knockouts, at least one gene immediately downstream exhibits a statistically significant change in mRNA expression. This approach may be useful in analyzing binding sites in a variety of organisms.
Evolutionary Strata on the Mouse X Chromosome Correspond to Strata on the Human X Chromosome
Authors: Sandstedt Sara A. , Tucker Priscilla K.
Published: February 2004

Lahn and Page previously observed that genes on the human X chromosome were physically arranged along the chromosome in “strata,” roughly ordered by degree ofdivergence from related genes on the Y chromosome. They hypothesized that this ordering results from a historical series of suppressions ofrecombination along the mammalian Y chromosome, thereby allowing formerly recombining X and Y chromosomal genes to diverge independently. Here predictions ofthis hypothesis are confirmed in a nonprimate mammalian order, Rodentia, through an analysis ofeight gene pairs from the X and Y chromosomes ofthe house mouse, Mus musculus. The mouse X chromosome has been rearranged relative to the human X, so strata were not found in the same physical order on the mouse X. However, based on synonymous evolutionary distances, X-linked genes in M. musculus fall into the same strata as orthologous genes in humans, as predicted. The boundary between strata 2 and 3 is statistically significant, but the boundary between strata 1 and 2 is not significant in mice. An analysis ofsmaller fragments of Smcy, Smcx, Zfy, and Zfx from seven species of Mus confirmed that the strata in Mus musculus were representative ofthe genus Mus.
The role of lipopolysaccharide in infectious bone resorption of periapical lesion
Authors: Hong Chi‐Yuan , Lin Sze‐Kwan , Kok Sang‐Heng , Cheng Shih‐Jung , Lee Ming‐Shu , Wang Tong‐Mei , Chen Chuan‐Shuo , Lin Li‐Deh , Wang Juo‐Song
Published: February 2004

Background:  The role of lipopolysaccharide (LPS) in periapical lesion‐induced bone resorption was investigated. Polymyxin B (PMB), a specific inhibitor of LPS, was evaluated to treat the apical lesion.

Methods:  Lipopolysaccharide isolated from two common endodontic pathogens, Fusobacterium nucleatum and Porphyromonas endodontalis, stimulated mouse macrophage (J774) to release interleukin‐1α (IL‐1α) and tumor necrosis factor‐α (TNF‐α) in a time‐dependent manner.

Results:  Combination of LPS further enhanced the stimulation. PMB inhibited these effects significantly. LPS also stimulated matrix metalloproteinase‐1 (MMP‐1) gene expression in J774, whereas anti‐IL‐1α and anti‐TNF‐α antibodies, as well as PMB, diminished this effect. A disease model of periapical lesion was established in Wistar rat. Administration of PMB reduced the extent of lesion‐associated bone resorption by 76% to approximately 80%, and simultaneously reduced the numbers of MMP‐1‐producing macrophages.

Conclusions:  It is suggested that LPS released from the infected root canal triggers the synthesis of IL‐1α and TNF‐α from macrophages. These pro‐inflammatory cytokines up‐regulate the production of MMP‐1 by macrophages to promote periapical bone resorption.
The Th1/Th2 immune‐type response of the recurrent aphthous ulceration analyzed by cDNA microarray
Authors: Borra R. C. , Andrade P. M. , Silva I. D. C. G. , Morgun A. , Weckx L. L. M. , Smirnova A. S. , Franco M.
Published: February 2004

Background:  The reduced ability to activate oral tolerance plays a role in the pathogenesis of some gastrointestinal inflammatory diseases. This activation may reflect a preferential reduction of a T‐helper (Th)2‐ or Th3‐type response. In recurrent aphthous ulceration (RAU), genetic and environmental factors may contribute to low tolerance, permitting a cytotoxic reaction against the oral epithelium. The cytokine profile has not permitted the definition of RAU as resulting from enhanced Th1 or Th2 responses. A cDNA microarray study would allow the identification of differentially expressed genes and provide a basis for classification of the immune response.

Methods:  The cDNA from 29 samples of aphthae and from 11 samples of normal mucosa from aphthae‐free volunteers were hybridized on microarray membranes with 1176 genes.

Results:  Forty‐one differentially expressed genes were identified, and a higher expression level of the Th1 gene cluster in RAU was found.

Conclusions:  Microarrays permitted us definition of the gene expression profile of the lesion and identify an increased Th1 activity in RAU lesions.
Serum interleukin‐8 level is a more sensitive marker than serum interleukin‐6 level in monitoring the disease activity of recurrent aphthous ulcerations
Authors: Sun Andy , Chang Yu‐Fong , Chia Jean‐San , Chiang Chun‐Pin
Published: February 2004

Background:  Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Interleukin (IL)‐8 is a pro‐inflammatory cytokine of host response to injury and inflammation. Our recent study has found that measurement of serum IL‐6 level can detect only 24% RAU patients with an abnormal serum level. In this study, we examined both the serum IL‐6 and IL‐8 levels in a group of RAU patients. The abilities of IL‐6 and IL‐8 to detect patients with an abnormal serum level were compared in order to find out whether IL‐8 was a more sensitive serum marker than IL‐6 in monitoring the disease activity of RAU.

Methods:  In this study, we used a solid‐phase, two‐site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL‐6 and IL‐8 in 146 patients with RAU, 9 patients with traumatic ulcers (TU), and 54 normal control (NC) subjects. Eighty‐two RAU patients, with the serum IL‐6 or IL‐8 levels higher than the upper limit of normal serum concentration, were treated with levamisole for 0.5–3.5 months, and their serum IL‐6 and IL‐8 levels were measured after treatment.

Results:  We found that 25% (37/146) RAU patients, as well as 33% (20/61) major‐type, 19% (13/69) minor‐type, and 25% (4/16) herpetiform‐type RAU patients, had a serum level of IL‐6 greater than the upper normal limit of 4.7 pg/ml. In contrast, 60% (87/146) RAU patients, as well as 59% (36/61) major‐type, 59% (41/69) minor‐type, and 63% (10/16) herpetiform‐type RAU patients, had a serum level of IL‐8 greater than the upper normal limit of 8.7 pg/ml. In 82 RAU patients with the serum IL‐6 or IL‐8 levels higher than the upper limit of normal serum concentration, treatment with levamisole for a period of 0.5–3.5 months could significantly reduce the serum IL‐6 level from 12.0 ± 1.6 to 3.0 ± 0.5 pg/ml (P < 0.001), and could significantly lower the serum IL‐8 level from 70.9 ± 11.2 to 13.8 ± 3.1 pg/ml (P < 0.001).

Conclusions:  Because measurement of serum IL‐8 level can detect 60% RAU patients with an abnormal serum level, while measurement of serum IL‐6 level can detect only 25% RAU patients with an abnormal serum level, we conclude that serum IL‐8 level is a more sensitive marker than serum IL‐6 level in monitoring the disease activity of RAU. Levamisole can modulate both the serum IL‐6 and IL‐8 levels in RAU patients. IL‐8, like IL‐6, is also a useful serum marker in evaluating therapeutic effects of levamisole on RAU patients.
The use of innovative ICT in the active pursuit of literacy
Authors: Watts M. , Lloyd C.
Published: February 2004

This paper investigates classroom interventions using a particular form of multimedia information and communication technology (ICT), and looks to study gains in pupil learning that accrue from its use. The research takes place in eight UK schools with 219, 11‐year‐old children (eight Year 6 classes). Work within the Literacy Hour is detailed in order to evaluate the effectiveness of a multimedia broadband educational communications system. The Literacy Hour is part of the UK Government's National Literacy Strategy: guideline requirements of schools to spend an hour a day on literacy to meet centrally established and monitored targets. The research data include pre‐ and post‐test assessments, along with 48 interviews with classroom teachers and pupils. The children are presented with a series of journalistic tasks and classroom activities that they resolve through the use of a compact and coordinated information system. The outcomes demonstrate that children can become self‐directive and very active – exploratory – learners in a very short period of time. They quickly enjoy the freedom and control that the system permits and through which they can be shown to enhance particular literacy skills. The lessons to be learned relate to the management and organisation of classroom teaching in the face of systems that promote rapid devolution of learning to the learner.
International Economic Sanctions Against a Dictator
Authors: Kaempfer William H. , Lowenberg Anton D. , Mertens William
Published: February 2004

Wintrobe's (1990, 1998) dictatorship model is adapted to examine the impacts of economic sanctions on an autocrat. It is shown that the dictator's choice of the level of power, and the quantities of loyalty and repression used as inputs in the production of power, are affected by the type and magnitude of sanctions and by the impact of sanctions on the political effectiveness of opposition groups. Sanctions have direct and indirect effects on the prices of loyalty and repression as well as potentially generating rents that might be captured either by the dictator or by the opposition.
Identification of an N‐terminal amino acid of the CLC‐3 chloride channel critical in phosphorylation‐dependent activation of a CaMKII‐activated chloride current
Authors: Robinson N. C. , Huang P. , Kaetzel M. A. , Lamb Fred S. , Nelson D. J.
Published: February 2004

CLC‐3, a member of the CLC family of chloride channels, mediates function in many cell types in the body. The multifunctional calcium–calmodulin‐dependent protein kinase II (CaMKII) has been shown to activate recombinant CLC‐3 stably expressed in tsA cells, a human embryonic kidney cell line derivative, and natively expressed channel protein in a human colonic tumour cell line T84. We examined the CaMKII‐dependent regulation of CLC‐3 in a smooth muscle cell model as well as in the human colonic tumour cell line, HT29, using whole‐cell voltage clamp. In CLC‐3‐expressing cells, we observed the activation of a Cl− conductance following intracellular introduction of the isolated autonomous CaMKII into the voltage‐clamped cell via the patch pipette. The CaMKII‐dependent Cl− conductance was not observed following exposure of the cells to 1 μm autocamtide inhibitory peptide (AIP), a selective inhibitor of CaMKII. Arterial smooth muscle cells express a robust CaMKII‐activated Cl− conductance; however, CLC‐3−/− cells did not. The N‐terminus of CLC‐3, which contains a CaMKII consensus sequence, was phosphorylated by CaMKII in vitro, and mutation of the serine at position 109 (S109A) abolished the CaMKII‐dependent Cl− conductance, indicating that this residue is important in the gating of CLC‐3 at the plasma membrane.
Kinetics of Mg2+ unblock of NMDA receptors: implications for spike‐timing dependent synaptic plasticity
Authors: Kampa Björn M. , Clements John , Jonas Peter , Stuart Greg J.
Published: February 2004

The time course of Mg2+ block and unblock of NMDA receptors (NMDARs) determines the extent they are activated by depolarization. Here, we directly measure the rate of NMDAR channel opening in response to depolarizations at different times after brief (1 ms) and sustained (4.6 s) applications of glutamate to nucleated patches from neocortical pyramidal neurons. The kinetics of Mg2+ unblock were found to be non‐instantaneous and complex, consisting of a prominent fast component (time constant ∼100 μs) and slower components (time constants 4 and ∼300 ms), the relative amplitudes of which depended on the timing of the depolarizing pulse. Fitting a kinetic model to these data indicated that Mg2+ not only blocks the NMDAR channel, but reduces both the open probability and affinity for glutamate, while enhancing desensitization. These effects slow the rate of NMDAR channel opening in response to depolarization in a time‐dependent manner such that the slower components of Mg2+ unblock are enhanced during depolarizations at later times after glutamate application. One physiological consequence of this is that brief depolarizations occurring earlier in time after glutamate application are better able to open NMDAR channels. This finding has important implications for spike‐timing‐dependent synaptic plasticity (STDP), where the precise (millisecond) timing of action potentials relative to synaptic inputs determines the magnitude and sign of changes in synaptic strength. Indeed, we find that STDP timing curves of NMDAR channel activation elicited by realistic dendritic action potential waveforms are narrower than expected assuming instantaneous Mg2+ unblock, indicating that slow Mg2+ unblock of NMDAR channels makes the STDP timing window more precise.
Nonlinear dynamics of a gas bubble in an incompressible elastic medium
Authors: Emelianov Stanislav Y. , Hamilton Mark F. , Ilinskii Yurii A. , Zabolotskaya Evgenia A.
Published: February 2004

A nonlinear model in the form of the Rayleigh–Plesset equation is developed for a gas bubble in an essentially incompressible elastic medium such as a tissue or rubberlike medium. Two constitutive laws for the elastic medium are considered: the Mooney potential, and Landau’s expansion of the strain energy density. These two constitutive laws are compared at quadratic order to obtain a relation between their respective elastic constants. Attention is devoted to the relative importance of shear stress on the bubble dynamics, allowing for the equilibrium gas pressure in the bubble to differ substantially from the pressure at infinity. The model for the bubble motion is approximated to quadratic order to assess the importance of shear stress in the surrounding medium relative to that of the gas pressure in the bubble. Relations are derived for the value of the shear wave speed at which the two contributions are comparable, which provide an assessment of when shear stress in the surrounding medium must be taken into account when modeling bubble dynamics.
Scattering of antiplane shear waves by layered circular elastic cylinder
Authors: Cai Liang-Wu
Published: February 2004

An exact analytical solution for the scattering of antiplane elastic waves by a layered elastic circular cylinder is obtained. The solution and its degenerate cases are compared with other simpler models of circular cylindrical scatterers. The effects of the geometrical and physical properties of the interphase are studied. Numerical results confirm the existence of a resonance mode in which the scatterer’s core undergoes a rigid-body motion when the outer layer of the scatterer is very compliant. This resonance mode has been attributed [Liu et al., Science 289, 1734 (2000)] to a new mechanism for the band gap formed in the extremely low frequency range for phononic crystals made of layered spherical scatterers. Numerical results also show the existence of a similar resonance mode when the outer layer of the scatterer has very high mass density.
Adjoint modeling for acoustic inversion
Authors: Hursky Paul , Porter Michael B. , Cornuelle B. D. , Hodgkiss W. S. , Kuperman W. A.
Published: February 2004

The use of adjoint modeling for acoustic inversion is investigated. An adjoint model is derived from a linearized forward propagation model to propagate data-model misfit at the observation points back through the medium to the medium perturbations not being accounted for in the model. This adjoint model can be used to aid in inverting for these unaccounted medium perturbations. Adjoint methods are being applied to a variety of inversion problems, but have not drawn much attention from the underwater acoustic community. This paper presents an application of adjoint methods to acoustic inversion. Inversions are demonstrated in simulation for both range-independent and range-dependent sound speed profiles using the adjoint of a parabolic equation model. Sensitivity and error analyses are discussed showing how the adjoint model enables calculations to be performed in the space of observations, rather than the often much larger space of model parameters. Using an adjoint model enables directions of steepest descent in the model parameters (what we invert for) to be calculated using far fewer modeling runs than if a forward model only were used.
Construction and control of a physiological articulatory model
Authors: Dang Jianwu , Honda Kiyoshi
Published: February 2004

A physiological articulatory model has been constructed using a fast computation method, which replicates midsagittal regions of the speech organs to simulate articulatory movements during speech. This study aims to improve the accuracy of modeling by using the displacement-based finite-element method and to develop a new approach for controlling the model. A “semicontinuum” tongue tissue model was realized by a discrete truss structure with continuum viscoelastic cylinders. Contractile effects of the muscles were systemically examined based on model simulations. The results indicated that each muscle drives the tongue toward an equilibrium position (EP) corresponding to the magnitude of the activation forces. The EPs shifted monotonically as the activation force increased. The monotonic shift revealed a unique and invariant mapping, referred to as an EP map, between a spatial position of the articulators and the muscle forces. This study proposes a control method for the articulatory model based on the EP maps, in which co-contractions of agonist and antagonist muscles are taken into account. By utilizing the co-contraction, the tongue tip and tongue dorsum can be controlled to reach their targets independently. Model simulation showed that the co-contraction of agonist and antagonist muscles could increase the stability of a system in dynamic control.
Comment on “Background noise in piezoresistive, electret condenser, and ceramic microphones” [J. Acoust. Soc. Am. 113, 3179–3187 (2003)] (L)
Authors: Brander Richard
Published: February 2004

This letter comments on the paper “Background noise in piezoresistive, electret condenser, and ceramic microphones” [J. Acoust. Soc. Am. 113, 3179–3187 (2003)], which found low-frequency-weighted noise in microphones. One possible mechanism for this type of noise is proposed.
A new method to predict the evolution of the power spectral density for a finite-amplitude sound wave
Authors: Menounou Penelope , Blackstock David T.
Published: February 2004

A method to predict the effect of nonlinearity on the power spectral density of a plane wave traveling in a thermoviscous fluid is presented. As opposed to time-domain methods, the method presented here is based directly on the power spectral density of the signal, not the signal itself. The Burgers equation is employed for the mathematical description of the combined effects of nonlinearity and dissipation. The Burgers equation is transformed into an infinite set of linear equations that describe the evolution of the joint moments of the signal. A method for solving this system of equations is presented. Only a finite number of equations is appropriately selected and solved by numerical means. For the method to be applied all appropriate joint moments must be known at the source. If the source condition has Gaussian characteristics (it is a Gaussian noise signal or a Gaussian stationary and ergodic stochastic process), then all the joint moments can be computed from the power spectral density of the signal at the source. Numerical results from the presented method are shown to be in good agreement with known analytical solutions in the preshock region for two benchmark cases: (i) sinusoidal source signal and (ii) a Gaussian stochastic process as the source condition.
Multiple focusing with adaptive time-reversal mirror
Authors: Kim J. S. , Shin K. C.
Published: February 2004

Recently, adaptivity was introduced to time-reversal mirror to steer the nulls, and referred to as an adaptive time-reversal mirror (ATRM) [J. S. Kim, H. C. Song, and W. A. Kuperman, J. Acoust. Soc. Am. 109, 1817–1825 (2001)]. In this study, ATRM is extended to simultaneous multiple focusing in an ocean waveguide. The multiple focusing is achieved by imposing a set of constraints in the formulation to find the weight vectors. The algorithm is applied to the long-range underwater acoustic communication to show, via simulation, that the simultaneous pulse compression at multiple receiving locations is achieved.
Vibration analysis on electromagnetic-resonance-ultrasound microscopy (ERUM) for determining localized elastic constants of solids
Authors: Tian Jiayong , Ogi Hirotsugu , Tada Toyokazu , Hirao Masahiko
Published: February 2004

In this paper we present a new acoustic-resonance microscopy, ElectromagneticResonance-Ultrasound Microscopy (ERUM), to measure the localized elastic stiffness of a solid material. It visualizes the resonance-frequency shift of vibrating piezoelectric crystal (langasite, La3Ga5SiO14) excited by an electric field from a solenoid coil. The acoustic coupling is made only at the tip of the crystal touching the specimen surface. Being based on the calibration for the specimen’s effective stiffness, the local elasticity is determined from the resonance frequencies of the crystal with the Rayleigh–Ritz method. An approximate model for the specimen’s effective stiffness predicts the shift of resonance frequencies, for which the conventional Hertz-contact model is improved. As an illustrating example, the mapping of Young’s modulus of a duplex stainless steel is presented, which shows good agreement with the existing study.
Ultrasound diffusion for crack depth determination in concrete
Authors: Ramamoorthy S. K. , Kane Y. , Turner J. A.
Published: February 2004

The determination of the depth of surface-breaking cracks in concrete specimens using an ultrasound diffusion technique is discussed. Experiments were carried out on precracked concrete specimens of varying crack depths (0%–40% of the specimen thickness). Contact transducers were placed at the specimen surface with source and receiver separated by the crack. Tone-burst excitations over a frequency range of 400–600 kHz were used. At these frequencies, ultrasound is scattered considerably by the heterogeneities in the concrete. In the limit of many scattering events, the evolution of energy may be modeled as a diffusion process. The arrival of the peak diffuse energy at the receiver is delayed due to the presence of crack. This delay is the prime indicator used for determining crack depth. Numerical and analytical analyses were also used for comparison. These results are in basic agreement with the experiments. In addition, these analyses are used to study the limits of this technique. In particular, it is shown that this technique is applicable to cracks greater than the scattering mean-free path, which is estimated at about 1 cm for these specimens. Aspects of practical implementation are also discussed.
Theoretical examination of ultrasonic pole figures via comparison with the results analyzed by finite element polycrystal model
Authors: Kobayashi Michiaki , Tang Shihua
Published: February 2004

The ultrasonic wave velocities in a polycrystalline aggregate are sensitively influenced by texture development due to plastic deformation. According to Sayer’s model, it is possible to construct ultrasonic pole figures via the crystallite orientation distribution function (CODF), which can be calculated by using ultrasonic wave velocities. In the previous papers, the theoretical modeling to simulate ultrasonic wave velocities propagating in solid materials under plastic deformation has been proposed by the authors and proved to be a good agreement with experimental results. Generally, wave velocities are dependent upon the propagating wave frequency; hence to evaluate texture development via ultrasonic pole figures it is necessary to examine an influence of frequency dependence on the ultrasonic wave velocities. In the present paper, the proposed theoretical modeling is applied to the texture characterization in polycrystalline aggregates of FCC metals under various plastic strain histories via ultrasonic pole figures, and also the frequency dependence is examined by using Granato–Lücke’s dislocation strings model. Then the simulated ultrasonic pole figures are compared with the pole figures analyzed by the finite element polycrystal model (FEPM). The good qualitative agreement between both results suggests the sufficient accuracy of our proposed theoretical modeling.