bluuebunny/crossref_metadata_2025 huggingface dataset:
Compound muscle action potentials during repetitive nerve stimulation
Authors: Asawa Teruko , Shindo Masaomi , Momoi Hiroki
Published: April 2004

When using repetitive nerve stimulation to examine neuromuscular transmission, the change in compound muscle action potential (CMAP) size is usually assessed by measurement of negative‐peak or peak‐to‐peak amplitude. Technological developments now allow automatic measurement of CMAP area, but some patients show increment of CMAP amplitude and decrement of CMAP area. This study systematically analyzed the changes in these CMAP parameters in 23 neurologically healthy subjects. CMAPs were recorded when the ulnar nerve was stimulated at frequencies of 1, 2, 5, 10, 20, 30, and 50 HZ (five pulses per train). CMAP amplitude showed significant increment within a train when stimulus frequency was above 5 HZ (probably due to increased muscle‐fiber conduction velocity), whereas CMAP area hardly changed at any frequencies. Measurement of CMAP area produces less ambiguous results than amplitude measurement in repetitive nerve stimulation studies. Muscle Nerve 29: 724–728, 2004
Muscle‐fiber conduction velocity estimated from surface emg signals during explosive dynamic contractions
Authors: Pozzo M. , Merlo E. , Farina D. , Antonutto G. , Merletti R. , Prampero P. E. Di
Published: April 2004

Muscle‐fiber conduction velocity (CV) was estimated from surface electromyographic (EMG) signals during isometric contractions and during short (150–200 ms), explosive, dynamic exercises. Surface EMG signals were recorded with four linear adhesive arrays from the vastus lateralis and medialis muscles of 12 healthy subjects. Isometric contractions were at linearly increasing force from 0% to 100% of the maximum. The dynamic contractions consisted of explosive efforts of the lower limb on a sledge ergometer. For the explosive contractions, muscle‐fiber CV was estimated in seven time‐windows located along the ascending time interval of the force. There was a significant correlation between CV values during the isometric ramp and explosive contractions (R = 0.75). Moreover, CV estimates increased significantly from (mean ± SD) 4.32 ± 0.46 m/s to 4.97 ± 0.45 m/s during the increasing‐force explosive task. It was concluded that CV can be estimated reliably during dynamic tasks involving fast limb movements and that, in these contractions, it may provide important information on motor‐unit control properties. Muscle Nerve 29: 823–833, 2004
Technology literature review: Quantitative sensory testing
Authors: Chong Peter Siao Tick , Cros Didier P.
Published: April 2004

The development of the personal computer has simplified the process of quantitating sensory thresholds using various testing algorithms. We reviewed the technical aspects and reproducibility of different methods to determine threshold for light touch‐pressure, vibration, thermal, and pain stimuli. Clinical uses and limitations of quantitative sensory testing (QST) were also reviewed. QST is a reliable psychophysical test of large‐ and small‐fiber sensory modalities. The results of QST are highly dependent on methodology and the full cooperation of the subject. QST has been shown to be reasonably reproducible over a period of days or weeks in normal subjects. The use of QST in research and patient care should be limited to instruments and their corresponding methodologies that have been shown to be reproducible. Literature data do not allow conclusions regarding the relative merits of individual QST instruments. Muscle Nerve 29: 734–747, 2004
Fracture toughness evaluation of polytetrafluoroethylene
Authors: Joyce James A.
Published: April 2004

The objective of this preliminary work was to explore the fracture resistance of polytetrafluoroethylene (PTFE) (DuPont tradename Teflon) as part of materials characterization work related to the development of “reactive” material projectiles. Little mechanical property data is available on this material since it is commonly used only as a coating material with the dominant properties being its low friction coefficient and high application temperature. Additional end products of the “7C” derivative, however, includes sheet, gaskets, bearing pads, piston rings, and diaphragms. In this work, standard ASTM E1820 fracture toughness specimens were machined from a 14‐mm‐thick sheet of this material obtained from NSWC Dahlgren Laboratory. These specimens were tested at three test temperatures and four test rates to determine if fracture would occur in this material, and if so, how the fracture toughness depends on the test temperature and specimen loading rate. Standard axial tensile specimens were also tested at quasi‐static and elevated loading rates at temperatures from ambient to −73°C. The major results are that while crack extension is difficult at ambient (20°C) temperature, for temperatures slightly below ambient, a rapid degradation of fracture resistance occurs. This reduction in fracture resistance is enhanced by rapid loading, and the material loses approximately 75% of its toughness (fracture energy absorption ability) at −18°C if the crack opening loading rate of the C(T) specimen approaches 0.25 m/s. Further reductions in temperature or increases in the loading rate appear to result in a reduced rate of degradation of fracture toughness.
Synthesis and properties of blue light‐emitting, silicon‐containing, regio‐ and stereoregular conjugated polymers
Authors: Sumiya Ken‐ichi , Kwak Giseop , Sanda Fumio , Masuda Toshio
Published: April 2004

This article concerns the hydrosilylation polyaddition of 1,4‐bis(dimethylsilyl)benzene (1) with 4,4′‐diethynylbiphenyl, 2,7‐diethynylfluorene (2b), and 2,6‐diethynylnaphthalene with RhI(PPh3)3 catalyst. Trans‐rich polymers with weight‐average molecular weights (Mw's) ranging from 19,000 to 25,000 were obtained by polyaddition in o‐Cl2C6H4 at 150–180 °C, whereas cis‐rich polymers with Mw's from 4300 to 34,000 were obtained in toluene at 0 °C–r.t. These polymers emitted blue light in 4–81% quantum yields. The cis polymers isomerized into trans polymers upon UV irradiation, whereas the trans polymers did not. The device having a layer of polymer trans‐3b obtained from 1 and 2b demonstrated electroluminescence without any dopant. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2774–2783, 2004
Synthesis and characterization of cis‐polybutadiene‐block‐syn‐polystyrene copolymers with a cyclopentadienyl titanium trichloride/modified methylaluminoxane catalyst
Authors: Ban Hoang The , Tsunogae Yasuo , Shiono Takeshi
Published: April 2004

This article reports a practical method for preparing cis‐polybutadiene‐block‐syn‐polystyrene (cis‐PB‐b‐syn‐PS) copolymers with long crystallizable syndiotactic polystyrene (syn‐PS) segments chemically bonded with high cis‐1,4‐polybutadiene segments through the addition of styrene (ST) to a cis‐specific 1,3‐butadiene (BD) living catalyst composed of cyclopentadienyl titanium trichloride (CpTiCl3) and modified methylaluminoxane (MMAO). The incorporation of ST into the living polybutadiene (PB) precursor remarkably depended on the polymerization temperature. A low temperature (−20 °C) suppressed the rate of ST incorporation, but a high temperature (50 °C) tended to decompose the livingness of the active species and enhance the rate of the aspecific ST polymerization initiated by MMAO. Consequently, temperatures of 0–25 °C seemed to be best for this copolymerization system. Because of the absence of ST livingness, the final products contained not only the block copolymer but also the homopolymers. Attempts to isolate the block copolymer were carried out with common solvent fractionation techniques, but the results were not sufficient. Cross‐fractionation chromatography was, therefore, used for the isolation of the cis‐PB‐b‐syn‐PS copolymer. The presence of long syn‐PS segments was confirmed by the observation of a strong endothermic peak at 260 °C in the differential scanning calorimetry curve. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2698–2704, 2004
Pessimism as a predictor of emotional morbidity one year following breast cancer surgery
Authors: Schou I. , Ekeberg Ø. , Ruland C.M. , Sandvik L. , Kåresen R.
Published: April 2004

The prevalence of and predictive factors for emotional morbidity (measured by the Hospital Anxiety and Depression Scale (HAD)) one year following surgery, with special focus on dispositional optimism/pessimism (measured by the Life Orientation Test (LOT‐R), was examined in 165 women, newly diagnosed with breast cancer. Patients characteristics, appraisal of cancer diagnosis, beliefs about treatment efficacy, treatment decision‐making participation, coping and emotional morbidity was assessed by self‐rating questionnaires.

Prevalence of anxiety and depression cases at time of diagnosis was 34 and 12%, respectively, and 26 and 9% after one year. Prevalence of emotional morbidity was significantly enlarged among pessimists at all assessments.

Pessimism was the strongest predictor for anxiety (OR: 0.86 C.I. 95% 0.77 – 0.95) and depression (OR: 0.83, C.I. 95% 0.73 – 0.95) one year following breast cancer surgery. Optimists and pessimists differed not only in regard to coping styles, but also in regards to predictors of emotional morbidity. Optimists experiencing anxiety at time of breast cancer diagnosis had about six times higher risk of experiencing anxiety after one year, compared to optimists without preoperative anxiety. For pessimists, the more pessimistic one was about one's overall future the higher risk for developing anxiety following one year of breast cancer surgery. Pessimists, who endorse helpless/hopeless coping style when receiving a diagnosis of breast cancer, had three times greater risk for experiencing depression one year after breast cancer surgery, than pessimists who did not. Health care professionals should therefore provide intervention for pessimists, as well as for patients with high anxiety scores at time of diagnosis. Copyright © 2003 John Wiley & Sons, Ltd.
Characteristics of cancer patients entering a smoking cessation program and correlates of quit motivation: implications for the development of tobacco control programs for cancer patients
Authors: Schnoll Robert A. , Rothman Randi L. , Newman Holly , Lerman Caryn , Miller Suzanne M. , Movsas Benjamin , Sherman Eric , Ridge John A. , Unger Michael , Langer Corey , Goldberg Melvyn , Scott Walter , Cheng Jonathan
Published: April 2004

Even though survival and quality of life are adversely affected by smoking among cancer patients, about one‐third of cancer patients who smoked prior to their diagnosis continue to smoke. One barrier to the provision of smoking cessation treatments to cancer patients is the paucity of data on the characteristics of cancer patients who continue to smoke and a lack of data on correlates of quit motivation in this population. This descriptive study assessed demographic, medical, smoking history, and psychological characteristics of cancer patients in a smoking cessation program (N=111) and examined these characteristics as correlates of quit motivation. Methods used by patients to quit smoking were also queried. We found that: (1) most patients are Caucasian, married, diagnosed with head and neck (versus lung) cancer, highly addicted to nicotine, and in the contemplation or preparation stage of change; (2) most patients attempt to quit smoking without formal treatment, although 33–50% have used the transdermal nicotine patch, nicotine gum, or bupropion; (3) depressive symptoms, low quitting self‐efficacy, low perceived risk, and low perceived benefits of quitting are prevalent among patients, but most patients do not endorse the perceived disadvantages of quitting or fatalistic beliefs; and (4) quit motivation is associated with higher quitting self‐efficacy, risk perceptions, and perceived benefits of quitting, lower tobacco use and nicotine addiction, and shorter time since diagnosis. These findings can help guide the development of smoking cessation interventions for cancer patients. Copyright © 2003 John Wiley & Sons, Ltd.
Prognostic value of depressive coping and depression in survival of lung cancer patients
Authors: Faller Hermann , Schmidt Michael
Published: April 2004

The aim of this investigation was to determine whether depressive coping and depression predict shorter survival among lung cancer patients. We conducted a prospective study using an inception cohort with a 3–5‐year follow‐up. The sample consisted of n = 59 (of n = 69 invited to participate) patients (mean age 65 years, S.D. = 9.7; 81% male) newly diagnosed with small cell lung cancer or non‐small cell lung cancer Stage III or IV who were scheduled for later chemotherapy and/or radiotherapy at a tertiary care centre. Patients were investigated after their diagnosis and before the beginning of treatment. Depressive coping and depression were assessed using standardized self‐report questionnaires (Freiburg Questionnaire of Coping with Illness; Hospital Anxiety and Depression Scale). Depressive coping was associated with shorter survival (hazard ratio 1.75, 95% confidence interval 1.04–2.93, p = 0.034) after adjusting for age, sex, stage, histological classification, and Karnofsky performance status but not treatment type, using the Cox proportional hazards regression. Depression, however, was not linked with survival (hazard ratio 1.05, 95% confidence interval 0.98–1.13, p = 0.18). To conclude, the prognostic value of depressive coping was partially confirmed, warranting further examination of the robustness of this relationship. Copyright © 2004 John Wiley & Sons, Ltd.
Molecular analysis of WFDC1/ps20 gene in prostate cancer
Authors: Watson J.E. Vivienne , Kamkar Shervin , James Karen , Kowbel David , Andaya Armann , Paris Pamela L. , Simko Jeffry , Carroll Peter , McAlhany Stephanie , Rowley David , Collins Colin
Published: April 2004

BACKGROUND

WFDC1/ps20 protein has been previously established as a growth suppressor of the prostate cancer cell line PC3. It maps to chromosome 16q23.1, a region of frequent loss of heterozygosity, familial association, and genomic loss in prostate cancer. We, therefore, chose to examine WFDC1/ps20 for mutations and expression changes in prostate cancer.

METHODS

DNA from 21 prostate cancer patients and 5 prostate cancer cell lines was screened for mutations in the WFDC1/ps20 gene by sequencing PCR products of each exon. An SphI polymorphism in the 5′ UTR was screened in 23 tumors, 22 normal adjacent prostate tissue samples, and 35 control DNAs. Expression of WFDC1/ps20 in different tissue types was examined by Northern blot and by PCR across a multi‐tissue cDNA panel. Expression patterns of WFDC1/ps20 in primary tumors were examined by full‐length RT‐PCR and products were cloned and sequenced to identify novel splice forms. Quantitative RT‐PCR analysis of WFDC1/ps20 was performed in a separate cohort of matched tumor/benign tissues.

RESULTS

No tumor‐associated mutations were identified in the coding region of WFDC1/ps20. A novel polymorphism was found in exon 6 in DNA from cell lines, tumors, and normal adjacent benign tissue. A novel splice form completely deleted for exon 3 was found in tumor and normal prostate RNA. Quantitative RT‐PCR demonstrated significant down regulation of WFDC1/ps20 in prostate tumors. Subdivision of normal tissue into stromal and epithelial compartments showed that WFDC1/ps20 expression correlates exponentially with the amount of stroma present.

CONCLUSIONS

WFDC1/ps20 is down regulated but not frequently mutated in prostate cancer. It is expressed predominantly in the normal stroma of the prostate. We, therefore, propose that WFDC1/ps20 may not be a classical tumor suppressor gene, but might play a role in the maintenance of the normal extra cellular matrix milieu in the prostate. © 2004 Wiley‐Liss, Inc.
Establishing the benefits of research experiences for undergraduates in the sciences: First findings from a three‐year study
Authors: Seymour Elaine , Hunter Anne‐Barrie , Laursen Sandra L. , DeAntoni Tracee
Published: April 2004

Descriptions of student‐identified benefits of undergraduate research experiences are drawn from analysis of 76 first‐round student interviews gathered at the end of summer 2000 at four participating liberal arts colleges (Grinnell, Harvey Mudd, Hope, and Wellesley). As part of the interview protocol, students commented on a checklist of possible benefits derived from the literature. They also added gains that were not on this list. Students were overwhelmingly positive: 91% of all statements referenced gains from their experiences. Few negative, ambivalent, or qualified assessments of their research experiences were offered. The benefits described were of seven different kinds. Expressed as percentages of all reported gains, they were personal/professional gains (28%); “thinking and working like a scientist” (28%); gains in various skills (19%); clarification/confirmation of career plans (including graduate school) (12%); enhanced career/graduate school preparation (9%); shifts in attitudes to learning and working as a researcher (4%); and other benefits (1%). © 2004 Wiley Periodicals, Inc.Sci Ed88:493–534, 2004
The sky as a topic in science education
Authors: Galili Igal , Weizman Ayelet , Cohen Ariel
Published: April 2004

The concepts of sky and visibility distance, as perceived by different learners, are investigated for the first time as a subject of a science education research. Mental models of students with regard to the subject were elicited. They were interpreted in terms of two‐level hierarchy: schemes and facets‐of‐knowledge (defined in the paper). Our results suggest that many students do not consider sky to be a scientific (physical) concept. The majority perceives the sky as having an oblate profile. Among the parameters that determine this profile were mentioned daytime, atmosphere, geometry of the situation, and weather conditions. The students hold two major explanatory views (schemes) with regard to the sky: “the sky is the atmosphere” and “the sky is the appearance of space.” With regard to the visibility distance, the two following schemes prevail: “vision weakens with the distance” and “natural obstacles determine vision distance.” No significant correlation was found between the views regarding the sky appearance and the vision distance. Students do not relate Moon illusion to the profile of sky or visibility distance. The notions of sky and visibility distance are argued for inclusion into science curriculum, and implications of the findings to a constructivist instruction of the considered concepts and phenomena are discussed. © 2004 Wiley Periodicals, Inc. Sci Ed 88:574–593, 2004
Assessment of changes in utero‐ovarian arterial impedance during the peri‐implantation period by Doppler sonography in women undergoing assisted reproduction
Authors: Chien L. W. , Lee W. S. , Au H. K. , Tzeng C. R.
Published: April 2004

Objective

To investigate changes in utero‐ovarian blood flow during the peri‐implantation period and their significance in successful embryo implantation.

Methods

A prospective longitudinal study was conducted in 317 women undergoing in‐vitro fertilization–embryo transfer (IVF–ET) treatment. All of them had at least one good‐quality embryo for transfer on the second or third day after oocyte retrieval. Measurement of endometrial thickness and color flow imaging with pulsed waveform analysis of uterine and ovarian arteries were performed before ET and 5–6 days after ET.

Results

There were no significant differences in the age of patients, duration of infertility or number of embryos transferred between women who became pregnant (n = 91) and those who did not (n = 226). There was no difference in mean endometrial thickness between the two groups before ET, while a thicker endometrium was found in women who had conceived compared with those who had not 5–6 days after ET (P = 0.02). Mean uterine arterial resistance index (RI) and pulsatility index (PI) values were significantly lower in the pregnant than in the non‐pregnant group before ET (P = 0.04 and P = 0.003, respectively), but no significant differences were found between the two groups 5–6 days after ET. In contrast, the mean ovarian arterial RI and PI values were similar between the two groups before ET, yet the pregnant group showed significantly lower RI and PI values compared with the non‐pregnant group 5–6 days after ET (P = 0.002 and P = 0.01, respectively). A significantly higher peak systolic velocity (PSV) of intraovarian vessels was also noted in the pregnant group 5–6 days after ET.

Conclusion

Different utero‐ovarian blood flow changes during the peri‐implantation period occur in conception and non‐conception cycles in women following IVF. Doppler assessment of uterine arterial resistance can help to determine a time interval within the menstrual cycle that is of optimal endometrial status for embryo implantation in assisted conception programs. Delay in achieving adequate uterine perfusion during the temporal window of embryo implantation may have an impact on endometrial receptivity. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Synthesis and Characterization of New Copper(I) Complexes Containing Thione Derivatives of 1, 2, 4‐Triazine. Crystal Structure of [Cu(PPh3)2(ATTO)]NO3 (ATTO = 4‐amino‐1, 2, 4‐triazin‐3(2H)‐thione‐5‐one)
Authors: Yazdanbakhsh Mohammad , Hakimi Mohammad , Heravi Majid M. , Ghassemzadeh Mitra , Neumüller Bernhard
Published: April 2004

The reaction of 4‐amino‐1, 2, 4‐triazin‐3(2H)‐thione‐5‐one (ATTO, 1) with [Cu(PPh3)2]NO3 in ethanol led to the complex [Cu(PPh3)2(ATTO)]NO3 (2). 2 was characterized by elemental analyses, IR, 1H NMR and Raman spectroscopy. A single‐crystal X‐ray diffraction of compound 2 revealed that ATTO acts as a bidentate ligand via its nitrogen and sulfur atoms. Crystal data for 2 at 20 °C: space group P21/n with a = 975.7(1), b = 1533.5(2), c = 2504.2(3) pm, β = 92.25(1)°, Z = 4, R1 = 0.0632.
Benign Positional Vertigo: Prognostic Factors
Authors: del Rio Maria , Arriaga Moisés A.
Published: April 2004

OBJECTIVE/HYPOTHESIS

We sought to assess prognostic factors associated with initial successful treatment and recurrence of benign paroxysmal positional vertigo (BPPV) with the canalith repositioning (CRP) maneuver with mastoid vibration.STUDY DESIGN AND SETTING:We conducted a retrospective chart review of 104 consecutive BPPV patients at a tertiary care referral center during 1999.

METHODS

The main outcome measures were resolution of BPPV and absence of nystagmus on Hallpike maneuver.

RESULTS

Ninety‐three patients (89.4%) experienced initial symptom resolution, and 21 of the initially successful patients had a recurrence (recurrence rate of 22.6%). Prior trauma or labyrinthitis was found to predict the lowest initial CRP success. Endolymphatic hydrops and central nervous system‐related dizziness as cofactors with BPPV were associated with the highest recurrence rates.

CONCLUSION AND SIGNIFICANCE

Specific concurrent otologic conditions are associated with different outcomes in BPPV. (Otolaryngol Head Neck Surg 2004;130:426‐9.)
Hearing Loss with Semicircular Canal Fistula in Exotoxin A‐Deficient Pseudomonas Otitis Media
Authors: Yunus Tariq M. , Molina Rolando M. , Prevatt Angela R. , Gajewski Byron J. , Sedwick Jack D. , Antonelli Patrick J.
Published: April 2004

OBJECTIVE

The study goal was to compare the severity of hearing loss with semicircular canal injury in the presence of otitis media (OM) due to an exotoxin A‐producing strain of Pseudomonas aeruginosa (PA+) and an exotoxin A‐deficient daughter strain (PA‐).

METHODS

PA+ or PA‐ was injected bilaterally into guinea pig ears. Three days later, unilateral lateral semicircular canal transection was performed. Hearing was tested before and after transection.

RESULTS

PA OM was induced in all injected ears. Significant elevation of click and 12‐kHz thresholds (P < 0.0001) were encountered in PA+‐infected ears. No significant threshold elevations were encountered in PA‐infected ears.

Conclusion

Hearing loss resulting from canal injury in the presence of Pseudomonas OM may be mediated by exotoxin A.

SIGNIFICANCE

Treatment to neutralize the effects of exotoxin A may minimize the risk of hearing loss with canal fistula in chronic OM.
Electron Microscopic Analysis of Biofilm on Endotracheal Tubes Removed from Intubated Neonates
Authors: Zur Karen B. , Mandell David L. , Gordon Ronald E. , Holzman Ian , Rothschild Michael A.
Published: April 2004

OBJECTIVE

To determine if the phenomenon of biofilm accumulation and associated microbial colonization occurs on the surface of endotracheal tubes in the region of the subglottis in neonates.

METHODS

Endotracheal tubes removed from 9 consecutive neonatal patients intubated for more than 12 hours were processed (range, 13 hours to 8 days). A sterile control tube was also processed. For each, the portion of the endotracheal tube that had been in contact with the subglottis was determined using a previously published nomogram. A 1‐cm‐long cross‐sectional segment of the endotracheal tube corresponding to the level of the subglottis was divided into 2 portions for both electron microscopy and aerobic/anaerobic cultures.

RESULTS

Two of 9 (22%) luminal surface cultures grewStaphylococcusspecies, 1 (11%) grew normal flora, and 6 (66%) had no growth. Three of 9 (33%) outer‐surface cultures grewStaphylococcusspecies, 1 (11%) had gram‐negative rods on staining but a sterile culture, and one enterococcal contaminant was found. Electron microscopy revealed that 8 of 9 inner lumen surfaces harbored bacteria and biofilm formation. All outer lumen surfaces had biofilm formation; 6 of 9 had bacterial colonization. There was no obvious difference in the appearance of the inner and outer tube surface accretions. No time‐dependent differences were noted except of the longest indwelling tube (8 days).

CONCLUSION

This study demonstrates for the first time the presence of biofilm on the outer surface of neonatal endotracheal tubes. The data suggest that the presence of bacteria and/or biofilm does not correlate with other traditional indicators of microbial colonization.
Rip channel development on nonbarred beaches: The importance of a lag in suspended‐sediment transport
Authors: Murray A. Brad
Published: April 2004

On approximately planar beaches, rip channel development is often preceded by a period in which jet‐like rip currents develop in apparently random locations, and dissipate after minutes to tens of minutes. The subsequent development of sharp‐edged, trough‐like channels extending across the surf zone suggests that rip currents on planar beaches cause local erosion. Conversely, channels are known to cause localized offshore‐directed flow, and once channels have formed on approximately planar beaches, rip currents no longer occur in apparently random locations, but are restricted to the locations of the channels. Apparently, the excavation of channels by rip currents on planar beaches triggers a positive feedback between the morphological development and the flow. However, theoretical analysis indicates that, when depth increases with distance from shore, and sediment transport is treated as a function only of local flow conditions, channel development in the vicinity of a rip current may not occur. In numerical simulations (using a “cellular” model of nonbathymetrically driven rip currents) in which sediment flux on a planar beach is driven by approximately realistic rip current velocity patterns, deposition occurs under parts of the rip currents (especially in the seaward half of the surf zone), and these “rip ridges” cause a negative feedback. In these simulations, as in most models treating surf zone sediment transport, sediment flux is assumed to be strictly a function of local hydrodynamic conditions. However, Observations of sediment‐laden rip‐current plumes extending well beyond the surf zone suggest that suspended sediment transport is not always in equilibrium with local conditions. Other simulations employ a treatment of suspended‐sediment transport that allows for a lag in the adjustment of fluxes to the changes in local hydrodynamic conditions that the sediment is advected through. With this nonlocal sediment‐transport, the flux of sediment out of the surf zone in a rip current is increased, ridges do not develop under any part of the rip currents, and the morphodynamic feedback becomes positive.
Modeling the climate response to a massive methane release from gas hydrates
Authors: Renssen H. , Beets C. J. , Fichefet T. , Goosse H. , Kroon D.
Published: April 2004

The climate response to a massive release of methane from gas hydrates is simulated in two 2500‐year‐long numerical experiments performed with a three‐dimensional, global coupled atmosphere‐sea ice‐ocean model of intermediate complexity. Two different equilibrium states were used as reference climates; the first state with preindustrial forcing conditions and the second state with a four times higher atmospheric CO2 concentration. These climates were perturbed by prescribing a methane emission scenario equivalent to that computed for the Paleocene/Eocene thermal maximum (PETM; ∼55.5 Ma), involving a sudden release of 1500 Gt of carbon into the atmosphere in 1000 years. In both cases, this produced rapid atmospheric warming (up to 10°C at high latitudes) and a reorganization of the global overturning ocean circulation. In the ocean, maximum warming (2–4°C) occurred at intermediate depths where methane hydrates are stored in the upper slope sediments, suggesting that further hydrate instability could result from the prescribed scenario.
Calcineurin-mediated Bad translocation regulates cyanide-induced neuronal apoptosis
Authors: SHOU Yan , LI Li , PRABHAKARAN Krishnan , BOROWITZ Joseph L. , ISOM Gary E.
Published: April 2004

In cyanide-induced apoptosis, an increase in cytosolic free Ca2+ and generation of reactive oxygen species are initiation stimuli for apoptotic cell death. Previous studies have shown that cyanide-stimulated translocation of Bax (Bcl-associated X protein) to mitochondria is linked with release of cytochrome c and subsequent activation of a caspase cascade [Shou, Li, Prabhakaran, Borowitz and Isom (2003) Toxicol. Sci. 75, 99–107]. In the present study, the relationship of the cyanide-induced increase in cytosolic free Ca2+ to activation of Bad (Bcl-2/Bcl-XL-antagonist, causing cell death) was determined in cortical cells. Bad is a Ca2+-sensitive pro-apoptotic Bcl-2 protein, which on activation translocates from cytosol to mitochondria to initiate cytochrome c release. In cultured primary cortical cells, cyanide produced a concentration- and time-dependent translocation of Bad from cytosol to mitochondria. Translocation occurred early in the apoptotic response, since mitochondrial Bad was detected within 1 h of cyanide treatment. Mitochondrial levels of the protein continued to increase up to 12 h post-cyanide exposure. Concurrent with Bad translocation, a Ca2+-sensitive increase in cellular calcineurin activity was observed. Increased cytosolic Ca2+ and calcineurin activation stimulated Bad translocation since BAPTA [bis-(o-aminophenoxy)ethane-N,N,N´,N´-tetra-acetic acid], an intracellular Ca2+ chelator, and cyclosporin A, a calcineurin inhibitor, significantly reduced translocation. BAPTA also blocked release of cytochrome c from mitochondria as well as apoptosis. Furthermore, treatment of cells with the calcineurin inhibitors cyclosporin A or FK506 blocked the apoptotic response, linking calcineurin activation and the subsequent translocation of Bad to cell death. These observations show that by inducing a rapid increase in cytosolic free Ca2+, cyanide can partially initiate the apoptotic cascade through a calcineurin-mediated translocation of Bad to mitochondria.
Quantitative analysis of nucleotide modulation of DNA binding by DnaC protein of Escherichia coli
Authors: BISWAS Subhasis B. , FLOWERS Stephen , BISWAS-FISS Esther E.
Published: April 2004

In this study, we have presented the first report of Escherichia coli DnaC protein binding to ssDNA (single stranded DNA) in an apparent hexameric form. DnaC protein transfers DnaB helicase onto a nascent chromosomal DNA replication fork at oriC, the origin of E. coli DNA replication. In eukaryotes, Cdc6 protein may play a similar role in the DNA helicase loading in the replication fork during replication initiation at the origin. We have analysed the DNA-binding properties of DnaC protein and a quantitative analysis of the nucleotide regulation of DnaC–DNA and DnaC–DnaB interactions using fluorescence anisotropy and affinity sensor analysis. DnaC protein bound to ssDNA with low to moderate affinity and the affinity was strictly modulated by nucleotides. DnaC bound ssDNA in the complete absence of nucleotides. The DNA-binding affinity was significantly increased in the presence of ATP, but not ATP[S]. In the presence of ADP, the binding affinity decreased approximately fifty-fold. Both anisotropy and biosensor analyses demonstrated that with DnaC protein, ATP facilitated ssDNA binding, whereas ADP facilitated its dissociation from ssDNA, which is a characteristic of an ATP/ADP switch. Both ssDNA and nucleotides modulate DnaB6•DnaC6 complex formation, which has significant implications in DnaC protein function. Based on the thermodynamic data provided in this study, we have proposed a mechanism of DnaB loading on to ssDNA by DnaC protein.
Structural model of carnitine palmitoyltransferase I based on the carnitine acetyltransferase crystal
Authors: MORILLAS Montserrat , LÓPEZ-VIÑAS Eduardo , VALENCIA Alfonso , SERRA Dolors , GÓMEZ-PUERTAS Paulino , HEGARDT Fausto G. , ASINS Guillermina
Published: April 2004

CPT I (carnitine palmitoyltransferase I) catalyses the conversion of palmitoyl-CoA into palmitoylcarnitine in the presence of l-carnitine, facilitating the entry of fatty acids into mitochondria. We propose a 3-D (three-dimensional) structural model for L-CPT I (liver CPT I), based on the similarity of this enzyme to the recently crystallized mouse carnitine acetyltransferase. The model includes 607 of the 773 amino acids of L-CPT I, and the positions of carnitine, CoA and the palmitoyl group were assigned by superposition and docking analysis. Functional analysis of this 3-D model included the mutagenesis of several amino acids in order to identify putative catalytic residues. Mutants D477A, D567A and E590D showed reduced L-CPT I activity. In addition, individual mutation of amino acids forming the conserved Ser685-Thr686-Ser687 motif abolished enzyme activity in mutants T686A and S687A and altered Km and the catalytic efficiency for carnitine in mutant S685A. We conclude that the catalytic residues are His473 and Asp477, while Ser687 probably stabilizes the transition state. Several conserved lysines, i.e. Lys455, Lys505, Lys560 and Lys561, were also mutated. Only mutants K455A and K560A showed decreases in activity of 50%. The model rationalizes the finding of nine natural mutations in patients with hereditary L-CPT I deficiencies.
Differential modulation of androgen receptor transcriptional activity by the nuclear receptor co-repressor (N-CoR)
Authors: BERREVOETS Cor A. , UMAR Arzu , TRAPMAN Jan , BRINKMANN Albert O.
Published: April 2004

Antiandrogens are widely used agents in the treatment of prostate cancer, as inhibitors of AR (androgen receptor) action. Although the precise mechanism of antiandrogen action is not yet elucidated, recent studies indicate the involvement of nuclear receptor co-repressors. In the present study, the regulation of AR transcriptional activity by N-CoR (nuclear receptor co-repressor), in the presence of different ligands, has been investigated. Increasing levels of N-CoR differentially affected the transcriptional activity of AR occupied with either agonistic or antagonistic ligands. Small amounts of co-transfected N-CoR repressed CPA (cyproterone acetate)- and mifepristone (RU486)-mediated AR activity, but did not affect agonist (R1881)-induced AR activity. Larger amounts of co-transfected N-CoR repressed AR activity for all ligands, and converted the partial agonists CPA and RU486 into strong AR antagonists. In the presence of the agonist R1881, co-expression of the p160 co-activator TIF2 (transcriptional intermediary factor 2) relieved N-CoR repression up to control levels. However, in the presence of RU486 and CPA, TIF2 did not functionally compete with N-CoR, suggesting that antagonist-bound AR has a preference for N-CoR. The AR mutation T877A (Thr877→Ala), which is frequently found in prostate cancer and affects the ligand-induced conformational change of the AR, considerably reduced the repressive action of N-CoR. The agonistic activities of CPA- and hydroxyflutamide-occupied T877A-AR were hardly affected by N-CoR, whereas TIF2 strongly enhanced their activities. These results indicate that lack of N-CoR action allows these antiandrogens to act as strong agonists on the mutant AR.
Proteasome inhibitors up-regulate haem oxygenase-1 gene expression: requirement of p38 MAPK (mitogen-activated protein kinase) activation but not of NF-kappaB (nuclear factor kappaB) inhibition
Authors: WU Wen-Tung , CHI Kwan-Hwa , HO Feng-Ming , TSAO Wei-Chia , LIN Wan-Wan
Published: April 2004

Regulation of intracellular protein stability by the ubiquitin-dependent proteasome system plays a crucial role in cell function. HO-1 (haem oxygenase) is a stress response protein, which confers cytoprotection against oxidative injury and provides a vital function in maintaining tissue homoeostasis. In the present study, we found a novel action of proteasome inhibitors MG132 and MG262 on HO-1 induction, and characterized the underlying mechanisms. MG132 (≥0.1 µM) treatment resulted in a marked time- and concentration-dependent induction of the steady-state level of HO-1 mRNA in RAW264.7 macrophages, followed by a corresponding increase in HO-1 protein. Actinomycin D and cycloheximide inhibited MG132-responsive HO-1 protein expression, indicating a requirement for transcription and de novo protein synthesis. The involvement of signal pathways in MG132-induced HO-1 gene expression was examined using chemical inhibitors. Antioxidant N-acetylcysteine and SB203580, an antioxidant and inhibitor of p38 MAPK (mitogen-activated protein kinase), abolished MG132-inducible HO-1 expression. Furthermore, MG132 activated the p38 MAPK pathway. The half-life of HO-1 protein was prolonged by MG132, indicating that the upregulation of HO-1 by proteasome inhibitor is partially attributable to the inhibition of protein degradation. MG132 can ablate IκBα degradation and NF-κB (nuclear factor κB) activation induced by lipopolysaccharide, similar to the effect of another NF-κB inhibitor pyrrolidine dithiocarbamate. We found HO-1 upregulation by MG132 and pyrrolidine dithiocarbamate is unrelated to their inhibition of NF-κB, since leptomycin B, another NF-κB inhibitor, did not elicit similar induction of HO-1. Taken together, we found a novel effect of proteasome inhibitor on induction of HO-1 expression. This action is ascribed to the activation of the p38 MAPK pathway, but is not dependent on NF-κB inhibition.
Modelling and bioinformatics studies of the human Kappa-class glutathione transferase predict a novel third glutathione transferase family with similarity to prokaryotic 2-hydroxychromene-2-carboxylate isomerases
Authors: ROBINSON Anna , HUTTLEY Gavin A. , BOOTH Hilary S. , BOARD Philip G.
Published: April 2004

The Kappa class of GSTs (glutathione transferases) comprises soluble enzymes originally isolated from the mitochondrial matrix of rats. We have characterized a Kappa class cDNA from human breast. The cDNA is derived from a single gene comprising eight exons and seven introns located on chromosome 7q34–35. Recombinant hGSTK1-1 was expressed in Escherichia coli as a homodimer (subunit molecular mass ~25.5 kDa). Significant glutathione-conjugating activity was found only with the model substrate CDNB (1-chloro-2,4-ditnitrobenzene). Hyperbolic kinetics were obtained for GSH (parameters: Kmapp, 3.3±0.95 mM; Vmaxapp, 21.4±1.8 µmol/min per mg of enzyme), while sigmoidal kinetics were obtained for CDNB (parameters: S0.5app, 1.5±1.0 mM; Vmaxapp, 40.3±0.3 µmol/min per mg of enzyme; Hill coefficient, 1.3), reflecting low affinities for both substrates. Sequence analyses, homology modelling and secondary structure predictions show that hGSTK1 has (a) most similarity to bacterial HCCA (2-hydroxychromene-2-carboxylate) isomerases and (b) a predicted C-terminal domain structure that is almost identical to that of bacterial disulphide-bond-forming DsbA oxidoreductase (root mean square deviation 0.5–0.6 Å). The structures of hGSTK1 and HCCA isomerase are predicted to possess a thioredoxin fold with a polyhelical domain (αx) embedded between the β-strands (βαβαxββα, where the underlined elements represent the N and C motifs of the thioredoxin fold), as occurs in the bacterial disulphide-bond-forming oxidoreductases. This is in contrast with the cytosolic GSTs, where the helical domain occurs exclusively at the C-terminus (βαβαββααx). Although hGSTK1-1 catalyses some typical GST reactions, we propose that it is structurally distinct from other classes of cytosolic GSTs. The present study suggests that the Kappa class may have arisen in prokaryotes well before the divergence of the cytosolic GSTs.
Transforming growth factor (TGF)beta, fibroblast growth factor (FGF) and retinoid signalling pathways promote pancreatic exocrine gene expression in mouse embryonic stem cells
Authors: SKOUDY Anouchka , ROVIRA Meritxell , SAVATIER Pierre , MARTIN Franz , LEÓN-QUINTO Trinidad , SORIA Bernat , REAL Francisco X.
Published: April 2004

Extracellular signalling cues play a major role in the activation of differentiation programmes. Mouse embryonic stem (ES) cells are pluripotent and can differentiate into a wide variety of specialized cells. Recently, protocols designed to induce endocrine pancreatic differentiation in vitro have been designed but little information is currently available concerning the potential of ES cells to differentiate into acinar pancreatic cells. By using conditioned media of cultured foetal pancreatic rudiments, we demonstrate that ES cells can respond in vitro to signalling pathways involved in exocrine development and differentiation. In particular, modulation of the hedgehog, transforming growth factor β, retinoid, and fibroblast growth factor pathways in ES cell-derived embryoid bodies (EB) resulted in increased levels of transcripts encoding pancreatic transcription factors and cytodifferentiation markers, as demonstrated by RT-PCR. In EB undergoing spontaneous differentiation, expression of the majority of the acinar genes (i.e. amylase, carboxypeptidase A and elastase) was induced after the expression of endocrine genes, as occurs in vivo during development. These data indicate that ES cells can undergo exocrine pancreatic differentiation with a kinetic pattern of expression reminiscent of pancreas development in vivo and that ES cells can be coaxed to express an acinar phenotype by activation of signalling pathways known to play a role in pancreatic development and differentiation.
Identification of a Ser/Thr cluster in the C-terminal domain of the human prostaglandin receptor EP4 that is essential for agonist-induced beta-arrestin1 recruitment but differs from the apparent principal phosphorylation site
Authors: NEUSCHÄFER-RUBE Frank , HERMOSILLA Ricardo , REHWALD Mathias , RÖNNSTRAND Lars , SCHÜLEIN Ralf , WERNSTEDT Christer , PÜSCHEL Gerhard Paul
Published: April 2004

hEP4-R (human prostaglandin E2 receptor, subtype EP4) is a Gs-linked heterotrimeric GPCR (G-protein-coupled receptor). It undergoes agonist-induced desensitization and internalization that depend on the presence of its C-terminal domain. Desensitization and internalization of GPCRs are often linked to agonist-induced β-arrestin complex formation, which is stabilized by phosphorylation. Subsequently β-arrestin uncouples the receptor from its G-protein and links it to the endocytotic machinery. The C-terminal domain of hEP4-R contains 38 Ser/Thr residues that represent potential phosphorylation sites. The present study aimed to analyse the relevance of these Ser/Thr residues for agonist-induced phosphorylation, interaction with β-arrestin and internalization. In response to agonist treatment, hEP4-R was phosphorylated. By analysis of proteolytic phosphopeptides of the wild-type receptor and mutants in which groups of Ser/Thr residues had been replaced by Ala, the principal phosphorylation site was mapped to a Ser/Thr-containing region comprising residues 370–382, the presence of which was necessary and sufficient to obtain full agonist-induced phosphorylation. A cluster of Ser/Thr residues (Ser-389–Ser-390–Thr-391–Ser-392) distal to this site, but not the principal phosphorylation site, was essential to allow agonist-induced recruitment of β-arrestin1. However, phosphorylation greatly enhanced the stability of the β-arrestin1–receptor complexes. For maximal agonist-induced internalization, phosphorylation of the principal phosphorylation site was not required, but both β-arrestin1 recruitment and the presence of Ser/Thr residues in the distal half of the C-terminal domain were necessary.
Conversion into GABA (gamma-aminobutyric acid) may reduce the capacity of l-glutamine as an insulin secretagogue
Authors: FERNÁNDEZ-PASCUAL Sergio , MUKALA-NSENGU-TSHIBANGU André , del RÍO Rafael MARTÍN , TAMARIT-RODRÍGUEZ Jorge
Published: April 2004

We have carried out a detailed examination of l-glutamine metabolism in rat islets in order to elucidate the paradoxical failure of l-glutamine to stimulate insulin secretion. l-Glutamine was converted by isolated islets into GABA (γ-aminobutyric acid), l-aspartate and l-glutamate. Saturation of the intracellular concentrations of all of these amino acids occurred at approx. 10 mmol/l l-glutamine, and their half-maximal values were attained at progressively increasing concentrations of l-glutamine (0.3 mmol/l for GABA; 0.5 and 1.0 mmol/l for Asp and Glu respectively). GABA accumulation accounted for most of the 14CO2 produced at various l-[U-14C]glutamine concentrations. Potentiation by l-glutamine of l-leucine-induced insulin secretion in perifused islets was suppressed by malonic acid dimethyl ester, was accompanied by a significant decrease in islet GABA accumulation, and was not modified in the presence of GABA receptor antagonists [50 µmol/l saclofen or 10 µmol/l (+)-bicuculline]. l-Leucine activated islet glutamate dehydrogenase activity, but had no effect on either glutamate decarboxylase or GABA transaminase activity, in islet homogenates. We conclude that (i) l-glutamine is metabolized preferentially to GABA and l-aspartate, which accumulate in islets, thus preventing its complete oxidation in the Krebs cycle, which accounts for its failure to stimulate insulin secretion; (ii) potentiation by l-glutamine of l-leucine-induced insulin secretion involves increased metabolism of l-glutamate and GABA via the Krebs cycle (glutamate dehydrogenase activation) and the GABA shunt (2-oxoglutarate availability for GABA transaminase) respectively, and (iii) islet release of GABA does not seem to play an important role in the modulation of the islet secretory response to the combination of l-leucine and l-glutamine.