bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basic studies of ductile failure processes and implications for fracture prediction
Authors: ZUO J. , SUTTON M. A. , DENG X. 
Published: February 2004

ABSTRACTFracture of ductile materials has frequently been observed to result from the nucleation, growth and coalescence of microscopic voids. Experimental and analytical studies have shown that both the stress constraint factor and the effective plastic strain play a significant role in the ductile failure process. Experimental results also suggest that these two parameters are not independent of each other at failure initiation. In this study, a methodology for characterizing the effect of stress constraint Am (which is defined to be the ratio of the mean stress and the effective stress Am=σm/σe) on ductile failure is proposed. This methodology is based on experimental evidence that shows the effective plastic strain at failure initiation has a one‐to‐one relationship with stress constraint. Numerical analyses based on plane strain and three‐dimensional unit‐cell models have been carried out to investigate failure initiation of the unit cell under different constraint conditions. Results from the numerical studies indicate (a) for each void volume fraction, there exists a local failure locus in terms of mesoscopic quantities, σm and σe, that adequately predict incipient local micro‐void link‐up, (b) the results are fully consistent with a failure criterion that maximizes mesoscopic effective stress for a constant level of stress constraint Am, (c) for high to moderate constraint Am, the link‐up envelope values for σm and σe are consistent with limit load conditions where the critical principal stress σ1c corresponds to the maximum principal stress in the loading history and (d) for low constraint, the link‐up envelope values for σm and σe correspond to link‐up conditions having high levels of plastic strain and a principal stress σ1 that is lower than the maximum value for this loading history. Thus, the results suggest that a two‐parameter ductile fracture criterion is plausible, such as critical crack opening displacement (COD) and stress constraint Am, for predicting the process of stable tearing in materials undergoing ductile void growth during the fracture process.
Overload analysis and Je‐based fatigue life prediction of spot‐welded auto seat belt anchors
Authors: LEE HYUNGIL , CHOI JINYONG 
Published: February 2004

ABSTRACTWe demonstrate the validity of Je, which comprehensively describes the effects of specimen geometry and loading type, in predicting the fatigue life of auto seat belt anchor panel. We first simplify the heat‐affected zone model to reduce the number of finite elements. We then establish finite‐element models reflecting the actual overload behaviour of three types of seat belt anchor specimens. Using elaborate finite‐element models, we obtain the effective crack‐driving parameter Je composed of its ductility‐dependent modal components. It is confirmed that the Je concept successfully predicts the fatigue life of multi‐spot‐welded panel structures represented by auto seat belt anchors here.
Estimation of fracture toughness of steel using chevron notched round bar specimens
Authors: RAY K. K. , PODDAR G. P. 
Published: February 2004

ABSTRACTA generalized methodology has been outlined in this paper for estimating the minimum normalized stress intensity factor (Y*min) of chevron notched round bar specimens, subjected to three‐point bend loading. Using such specimens, a series of fracture toughness tests have been carried out for the first time on two steels. The major inferences drawn from this investigation are: (i) reproducible fracture toughness values can be achieved using chevron notched rod specimens of identical configuration and (ii) the estimated magnitudes of fracture toughness obtained by using chevron notched rod specimens are in good agreement with those achieved by using chevron notched rectangular bar specimens of the same material.
Distinct subcellular targeting of fluorescent nicotinic α3β4 and serotoninergic 5‐HT3A receptors in hippocampal neurons
Authors: Grailhe Régis , De Carvalho Lia Prado , Paas Yoav , Le Poupon Chantal , Soudant Martine , Bregestovski Piotr , Changeux Jean‐Pierre , Corringer Pierre‐Jean 
Published: February 2004

AbstractThe nicotinic acetylcholine receptors (nAChRs) and the 5‐HT3 serotonin receptor subtype belong to a superfamily of neurotransmitter‐gated ion channels involved in fast synaptic communication throughout the nervous system. Their trafficking to the neuron plasmalemma, as well as their targeting to specific subcellular compartments, is critical for understanding their physiological role. In order to investigate the cellular distribution of these receptors, we tagged the N‐termini of α3β4‐nAChR subunits and the 5‐HT3AR subunit with cyan and yellow fluorescent proteins (CFP, YFP). The fusion subunits were coexpressed in human embryonic kidney (HEK‐293) cells, where they assemble into functional receptor channels, as well as in primary cultures of hippocampal neurons. Fluorescence microscopy of living cells revealed that the heteropentameric α3CFP‐β4 and YFP‐α3β4 receptors are mainly distributed in the endoplasmic reticulum, while the homopentameric YFP‐5‐HT3A receptor was localized both to the plasma membrane and within intracellular compartments. Moreover, the YFP‐5‐HT3A receptor was found to be targeted to the micropodia in HEK‐293 cells and to the dendritic spines in hippocampal neurons, where it could be accessed by extracellularly applied specific fluorescent probes. The efficient targeting of the YFP‐5‐HT3A to the cytoplasmic membrane is in line with the large serotonin‐elicited currents (nA range) measured by whole‐cell voltage‐clamp recordings in transfected HEK‐293 cells. In contrast, α3β4‐nAChRs expressed in the same cells yielded weaker ACh‐evoked responses. Taken together, the fluorescent and electrophysiological studies presented here demonstrate the predominant intracellular location of α3β4‐nACh receptors and the predominant expression of the 5‐HT3AR in dendritic surface loci.
Resetting the brain clock: time course and localization of mPER1 and mPER2 protein expression in suprachiasmatic nuclei during phase shifts
Authors: Yan Lily , Silver Rae 
Published: February 2004

AbstractThe mechanism whereby brief light pulses reset the mammalian circadian clock involves acute Per gene induction. In a previous study we investigated light‐induced expression of mPer1 and mPer2 mRNA in the suprachiasmatic nuclei (SCN), with the aim of understanding the relationship between gene expression and behavioural phase shifts. In the present study, we examine the protein products of mPer1 and mPer2 genes in the core and shell region of SCN for 34 h following a phase‐shifting light pulse, in order to further explore the molecular mechanism of photic entrainment. The results indicate that, during the delay zone of the phase response curve, while endogenous levels of mPER1 and mPER2 protein are falling, a light pulse produces an increase in the expression of both proteins. In contrast, during the advance zone of the phase response curve, while levels of endogenous mPER1 and mPER2 proteins are rising, a light pulse results in a further increase in mPER1 but not mPER2 protein. The regional distribution of mPER1 and mPER2 protein in the SCN follows the same pattern as their respective mRNAs, with mPER1 expression in the shell region of SCN correlated with phase advances and mPER2 in the shell region correlated with phase delays.
An immunogold investigation of the distribution of GABA and glycine in nerve terminals on the somata of spherical bushy cells in the anteroventral cochlear nucleus of guinea pig
Authors: Mahendrasingam S. , Wallam C. A. , Polwart A. , Hackney C. M. 
Published: February 2004

AbstractSpherical bushy neurons in the anteroventral cochlear nucleus receive glutamatergic primary terminals from the cochlear nerve and terminals of noncochlear (i.e. nonprimary) origin, many of which colocalize gamma‐aminobutyric acid (GABA) and glycine. Here the relationship between GABA and glycine in these terminals has been investigated using postembedding immunogold labelling. A significant negative correlation was found between the density of terminal labelling for GABA and for glycine in four guinea pigs. Terminals could be divided into three categories, GABA‐only, glycine‐only, or colocalizing depending on whether they had a significantly higher labelling density for either amino acid than the primary terminals. The overall labelling density in all four animals was significantly greater for GABA in GABA‐only terminals than colocalizing ones but similar for glycine in both. Within the terminals, the labelling density over synaptic vesicles, nonvesicular regions of cytoplasm and mitochondria was also investigated. No significant difference was detected in the labelling density of vesicles compared with nonvesicular regions for either amino acid. However, a significant difference was found between the overall labelling density over mitochondria and nonvesicular regions for both. There was also significantly more mitochondrial GABA labelling in GABA‐only terminals compared to colocalizing terminals but mitochondrial glycine labelling was similar in glycine‐only and colocalizing terminals. Thus the level of GABA is higher in single than in colocalizing terminals, particularly in the mitochondria, but similar for glycine in both. It is possible therefore that the presence of glycine affects the level of GABA in the nonprimary terminals but that the presence of GABA does not affect the level of glycine.
Postnatal regulation by monoamines of vasopressin expression in the neuroendocrine hypothalamus of MAO‐A‐deficient mice
Authors: Vacher Claire‐Marie , Calas André , Maltonti Fabrice , Hardin‐Pouzet Hélène 
Published: February 2004

AbstractWe studied the influence of noradrenaline (NA) and serotonin (5‐HT) on arginine–vasopressin (AVP) expression in the mouse neuroendocrine hypothalamus during the postnatal period. We used 11‐day‐old transgenic Tg8 mice knock‐out for the monoamine oxidase A gene, which are characterized by increased amounts of NA (two‐fold) and 5‐HT (nine‐fold) in the brain compared with wild‐type littermates. AVP expression, determined by enzyme immunoassay and in situ hybridization, was increased in the suprachiasmatic nucleus (SCN), decreased in the supraoptic nucleus (SON), and unchanged in the paraventricular nucleus of Tg8 mice compared with wild‐types. Inhibiting NA synthesis by injecting α‐methylparatyrosine to Tg8 mice, AVP levels were decreased in the SCN but increased in the SON. Moreover, the administration of parachlorophenylalanine, a 5‐HT synthesis inhibitor, was associated with increased AVP contents in the SCN only. Together, these data show a marked region‐specific sensitivity of AVP expression to NA and 5‐HT during the postnatal period in the mouse hypothalamus.
Auditory perception vs. recognition: representation of complex communication sounds in the mouse auditory cortical fields
Authors: Geissler Diana B. , Ehret Günter 
Published: February 2004

AbstractDetails of brain areas for acoustical Gestalt perception and the recognition of species‐specific vocalizations are not known. Here we show how spectral properties and the recognition of the acoustical Gestalt of wriggling calls of mouse pups based on a temporal property are represented in auditory cortical fields and an association area (dorsal field) of the pups' mothers. We stimulated either with a call model releasing maternal behaviour at a high rate (call recognition) or with two models of low behavioural significance (perception without recognition). Brain activation was quantified using c‐Fos immunocytochemistry, counting Fos‐positive cells in electrophysiologically mapped auditory cortical fields and the dorsal field. A frequency‐specific labelling in two primary auditory fields is related to call perception but not to the discrimination of the biological significance of the call models used. Labelling related to call recognition is present in the second auditory field (AII). A left hemisphere advantage of labelling in the dorsoposterior field seems to reflect an integration of call recognition with maternal responsiveness. The dorsal field is activated only in the left hemisphere. The spatial extent of Fos‐positive cells within the auditory cortex and its fields is larger in the left than in the right hemisphere. Our data show that a left hemisphere advantage in processing of a species‐specific vocalization up to recognition is present in mice. The differential representation of vocalizations of high vs. low biological significance, as seen only in higher‐order and not in primary fields of the auditory cortex, is discussed in the context of perceptual strategies.
AMPA receptor properties and coexpression with sodium–calcium exchangers in rat hypothalamic neurons
Authors: Sergeeva O. A. , Amberger B. T. , Vorobjev V. S. , Eriksson K. S. , Haas H. L. 
Published: February 2004

AbstractThe histaminergic tuberomamillary (TM) nucleus, a center for the regulation of wakefulness, is excited by glutamatergic, aminergic and peptidergic inputs. AMPA receptor properties in relation to their expression were investigated in acutely isolated TM neurons with the help of whole‐cell patch‐clamp recordings combined with single‐cell RT‐PCR. The mRNAs encoding for the AMPA receptor GluR2 (100% of the neurons) and GluR1 (75%) were the most frequently detected, followed by the mRNA for GluR4 (56%), whereas GluR3 cDNA amplification did not yield a PCR product in any neuron. Flip splice variants prevailed over flop, in keeping with a strong glutamate‐response potentiation by cyclothiazide. The expression pattern of AMPA subunits in their two splice variants was correlated with the different subtypes of Na+/Ca2+ (NCX) and Na+/Ca2+/K+ (NCKX) exchangers: glutamate receptor subunits GluR1–4 displayed no coordinated pattern with NCX. However, NCKX2 mRNA occurred only in TM cells with a fast desensitizing glutamate response, where it was coexpressed with the GluR4 subunit in the flop splice variant. NCKX3 mRNA was detected in neurons with fast or slow desensitization of glutamate responses. AMPA receptors in TM neurons were Ca2+‐impermeable. As reverse Na+/Ca2+ exchange contributes to the immediate rise in intracellular calcium resulting from glutamate receptor activation, we suggest that the coordinated expression of NCKX2 with the fast desensitizing AMPA receptor‐type reflects either a receptor–exchanger coupling or separate mechanisms for maintaining calcium homeostasis in neurons with fast or slow glutamate responses.
Pattern motion is present in V1 of awake but not anaesthetized monkeys
Authors: Guo Kun , Benson Philip J. , Blakemore Colin 
Published: February 2004

AbstractWe compared responses of neurons, recorded in striate cortex (area V1) of awake, fixating monkeys, to a single drifting grating with those to a ‘plaid’ pattern comprised of two superimposed drifting gratings separated in orientation by 90°. Five out of 54 (9%) of V1 direction selective neurons responded to the direction of motion of the whole pattern [pattern motion (PM) selectivity]. Tuning curves for plaid stimuli were similar in both optimum direction and width of tuning to those for single gratings. Twenty nine out of 54 (54%) responded simply to the motion of individual orientated gratings within the pattern [component motion (CM) selectivity]. The remaining 37% (20/54) neurons were unclassified. In control experiments, 39 direction selective neurons were recorded in area V1 of anaesthetized monkey and cats. Unlike area V1 in behaving monkeys, none of these neurons exhibited PM selectivity to the drifting plaids. Twenty eight out of 39 (72%) of them responded to the direction of the component gratings and were classified as CM selectivity. Our results indicate that although most V1 neurons are CM selective, as described in anaesthetized animals, a subpopulation is clearly PM selective in behaving monkeys, reflecting integration of locally derived motion signals. Neurons in V1 therefore carry signals that may contribute to pattern motion processing and perception. This perceptual interpretation in V1 might depend much more critically on information integration mechanisms that only function properly in awake, perceiving animals.
Spatially and temporally restricted chemoattractive and chemorepulsive cues direct the formation of the nigro‐striatal circuit
Authors: Gates Monte A. , Coupe Victoria M. , Torres Eduardo M. , Fricker‐Gates Rosemary A. , Dunnett Stephen B. 
Published: February 2004

AbstractIdentifying cellular and molecular mechanisms that direct the formation of circuits during development is thought to be the key to reconstructing circuitry lost in adulthood to neurodegenerative disorders or common traumatic injuries. Here we have tested whether brain regions situated in and around the developing nigro‐striatal pathway have particular chemoattractive or chemorepulsive effects on mesencephalic dopamine axons, and whether these effects are temporally restricted. Mesencephalic explants from embryonic day (E)12 rats were either cultured alone or with coexplants from the embryonic, postnatal or adult medial forebrain bundle region (MFB), striatum, cortex, brain stem or thalamus. Statistical analysis of axon growth responses revealed a potent chemoattraction to the early embryonic MFB (i.e. E12–15) that diminished (temporally) in concert with the emergence of chemoattraction to the striatum in the late embryonic period (i.e. E19+). Repulsive responses by dopaminergic axons were obvious in cocultures with embryonic brain stem and cortex, however, there was no effect by the thalamus. Such results suggest that the nigro‐striatal circuit is formed via spatially and temporally distributed chemoattractive and chemorepulsive elements that: (i) orientate the circuit in a rostral direction (via brain stem repulsion); (ii) initiate outgrowth (via MFB attraction); (iii) prevent growth beyond the target region (via cortical repulsion); and (iv) facilitate target innervation (via striatal chemoattraction). Subsequent studies will focus on identifying genes responsible for these events so that their products may be exploited to increase the integration of neuronal transplants to the mature brain, or provide a means to (re)establish the nigro‐striatal circuit in vivo.
Intravesical administration of gemcitabine in superficial bladder cancer: a phase I study with pharmacodynamic evaluation
Authors: De Berardinis E. , Antonini G. , Peters G.J. , Loves W.J.P. , Van Der Born K. , Codacci‐Pisanelli G. , Di Silverio F. 
Published: February 2004

OBJECTIVETo determine, in a phase I trial, the local and systemic toxicity and pharmacodynamics of intravesical gemcitabine in patients with superficial bladder cancer.PATIENTS AND METHODSTwelve patients with histologically confirmed carcinoma localized to the bladder wall (stage T1 or Ta) resistant to previous administration of anticancer drugs and/or of bacille Calmette‐Guérin were enrolled. They initially received intravesical gemcitabine starting at 500 mg and increased in 500 mg increments to 2000 mg. Three patients were treated at each dose level.RESULTSThere was no evidence of systemic toxicity and local toxicity was minimal. A pharmacological evaluation showed that gemcitabine was undetectable in plasma and its inactive metabolite (2′,2′‐difluorodeoxyuridine) was present at a mean (sd) concentration of 1.39 (1.05) µmol/L. Deoxycytidine kinase was present in tumour tissue samples, and its activity was 27.3 (12.6) pmol/h/mg tissue; deoxycytidine deaminase activity varied from undetectable to 616 pmol/h/mg tissue.CONCLUSIONIntravesical gemcitabine appears to be well tolerated with no systemic and minimal local toxicity even at the highest dose (2000 mg). A phase II trial of intravesical gemcitabine at 2000 mg given weekly for six consecutive weeks is now in progress in patients with superficial bladder cancer.
Characterizing prostatic adenocarcinomas in men with a serum prostate specific antigen level of <4.0 ng/mL
Authors: Sokoloff M.H. , Yang X.J. , Fumo M. , Mhoon D. , Brendler C.B. 
Published: February 2004

OBJECTIVETo characterize prostate cancer in men undergoing radical prostatectomy who have a prostate‐specific antigen (PSA) level of < 4.0 ng/mL, hypothesising that a low PSA is not caused by diminished tumour production of PSA, nor does it signify clinically insignificant disease.PATIENTS AND METHODSSeventy‐nine men (mean age 59.3 years, range 43–77) with a PSA level of < 4.0 ng/mL were identified from 702 who had a radical prostatectomy between 1994 and 2000. Demographic and clinical data were analysed; pathological specimens were evaluated by routine haematoxylin and eosin staining and immunohistochemistry with anti‐PSA antibody, for both pathological staging and grading, and for the presence of PSA production. Tumours were classified as ‘clinically insignificant’ if the tumour volume was < 0.5 mL and the Gleason score < 7.RESULTSThe mean (sd, range) preoperative PSA level was 3.04 (0.85, 0.8–3.8) ng/mL. Indications for biopsy included an abnormal digital rectal examination (61%), a PSA velocity of >0.75 ng/mL/year (12%), a strong family history of prostate cancer (3%), obstructive urinary symptoms (2%), or no obvious indication (23%). Thirty‐eight (48%) tumours were clinically insignificant. Of 41 clinically significant cancers, 13 had a final Gleason score of ≥ 7, 20 had extraprostatic extension and 11 had a tumour volume of ≥ 10 mL. Of the 79 prostate cancer specimens 78 stained strongly for PSA; the exception was a Gleason 9 tumour. With a mean (range) follow‐up of 3.5 (0.18–6) years only one patient had a biochemical recurrence (PSA ≥ 0.1 ng/mL).CONCLUSIONSMost prostate cancers in men with a PSA level of < 4.0 ng/mL are clinically significant and PSA‐producing. Many of these tumours are high‐grade, high‐volume and extraprostatic. We are currently exploring factors to explain why serum PSA is not elevated in these men, including tumour location, pattern of invasion and microvessel density.
The benefits of radical prostatectomy beyond cancer control in symptomatic men with prostate cancer
Authors: Kumar V. , Toussi H. , Marr C. , Hough C. , Javle P. 
Published: February 2004

OBJECTIVETo evaluate lower urinary tract symptoms (LUTS) and the symptom‐associated quality of life (QoL) after radical prostatectomy.PATIENTS AND METHODSWe carried out a prospective study (January 1999 to March 2001) of 50 consecutive men initially assessed in the nurse‐led prostate assessment clinic for their LUTS and subsequently diagnosed to have localized prostate cancer. They had a radical retropubic prostatectomy and were assessed before, 3 and 6 months after surgery with a self‐administered International Prostate Symptom Score (IPSS) and QoL questionnaires, and measurements of urinary flow rate and postvoid residual urinary (PVR) volumes. Finally, each patient completed a self‐administered continence questionnaire at 6 weeks, 3 and 6 months after surgery.RESULTSIn men with moderate to severe LUTS before surgery there were significant improvements in total IPSS, symptom‐associated QoL, mean peak flow rate and PVR (P < 0.05). However, in eight men with mild LUTS, although there was a 33% improvement in the total symptom score, it was not statistically significant. Thirty‐eight patients reported complete continence, nine had infrequent stress leaks only on heavy physical activity, and the remaining three used < 2 pads/day for protection before heavy physical activity at 3 months after surgery.CONCLUSIONSRadical prostatectomy provides major benefits to men with LUTS besides cancer control. These data are important in counselling patients about the treatment options, especially in view of the current enthusiasm for brachytherapy and conformal radiotherapy, which may worsen LUTS.