bluuebunny/crossref_metadata_2025 huggingface dataset:
A very compact electromagnetic bandgap structure for suppressing surface waves in integrated circuits
Authors: Fu Yunqi , Yuan Naichang , Zhang Guohua
Published: April 2004

A very compact electromagnetic bandgap structure is presented for integrated‐circuits applications. This structure, which is one kind of high‐impedance surface with periodic interdigital elements, is adopted to increase the fringe capacitor in order to compress the overall size of the high‐impedance surface. Its design uses the effective‐circuit model. The measured results show that a 30% to 40% size reduction can be obtained. This will be very valuable for practical applications. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 455–457, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20169
Compact ridged‐waveguide bandpass filters and diplexers
Authors: Shelkovnikov Aleksandr , Goussetis George , Budimir Djuradj
Published: April 2004

A ridged‐waveguide diplexer incorporating integrated compact ridged‐waveguide filters and a ridged‐waveguide T‐junction is presented. The compact size of the filter is achieved by integrating a bandpass periodic filter, and a low‐pass structure is used in order to suppress spurious responses. Simulation using the mode‐matching method has been carried out for ridged‐waveguide filters and T junctions and the results are presented. The measured results are in good agreement with the simulated results. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 465–467, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20173
Equivalent electric circuit of the P‐i‐N photodiode for the pulse incident excitation
Authors: Lazović Miomira V. , Matavulj Petar S. , Radunović Jovan B.
Published: April 2004

An equivalent electric circuit of a P‐i‐N photodiode, for the case of the pulse‐light excitation, is derived and incorporated using SPICE. We consider only nonlinearity, which is the result of the change of the photodiode's reverse‐bias voltage. We compare our SPICE model with a previously published analytical model. The results obtained prove the superiority of the derived model, which has potential application in comprehensive OEIC modeling. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 468–471, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20174
Compact triple‐band planar inverted‐F antenna for mobile handsets
Authors: Qi Dongsheng , Li Binhong , Liu Haitao
Published: April 2004

A novel compact triple‐band (GSM, DCS, and ISM) planar inverted‐F antenna is presented. A prototype was constructed and studied. The S11 parameters are measured and bandwidths of 3.4%, 10.3%, and 2.1% are obtained for the corresponding band, respectively. For practical application, the presence of the plastic case and the hand were considered, and the resulting data of their influence were obtained and discussed. The radiation patterns and gains are also measured. All the results show that this type of PIFA is suitable for mobile‐communication applications. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 483–486, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20179
High‐conversion‐gain millimeter‐wave ×4 subharmonic mixer with cascode 4th‐harmonic generator
Authors: An Dan , Kim Sung Chan , Sul Woo Suk , Han Hyo Jong , Park Hyung Moo , Rhee Jin Koo
Published: April 2004

In this paper, a millimeter‐wave ×4 subharmonic mixer has been designed and fabricated. The cascode 4th‐harmonic generator is proposed for high conversion gain. The measurement of an LO power of 13 dBm shows a conversion gain of 3.4 dB, which is one of the best conversion gains at 60.4 GHz. Isolations of LO to IF and LO to RF were obtained −53.6 and −46.2 dB, respectively. The high conversion gain achieved in this work is the first to be reported among millimeter‐wave subharmonic mixers. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 490–493, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20181
Zn‐diffused LiNbO3 2 × 2 balanced‐bridge optical switch with post thermal‐treatment
Authors: Twu Ruey‐Ching
Published: April 2004

A Zn‐diffused 2 × 2 balanced‐bridge optical switch is demonstrated on a Z‐cut LiNbO3 substrate for the first time. A post thermal‐treatment is used for precisely maintaining the 3‐dB‐power division of the two directional couplers in the device. The crosstalk ratio of both output waveguides is about −23 dB, while the measured propagation loss of a straight‐channel waveguide is kept within the range of 1.1–1.25 dB/cm. In the design, without using electrically controllable couplers as 3‐dB splitters or combiners, the total device length can be reduced to 18 mm. The switching voltage‐length product is 8.5 V‐cm for the TM polarized light at 1.32 μm. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 493–496, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20182
MRI investigation of the threshold for thermally induced blood–brain barrier disruption and brain tissue damage in the rabbit brain
Authors: McDannold Nathan , Vykhodtseva Natalia , Jolesz Ferenc A. , Hynynen Kullervo
Published: April 2004

The ability of MRI‐derived thermometry to predict thermally induced tissue changes in the brain was tested, and the thermal thresholds for blood–brain barrier (BBB) disruption and brain tissue damage were estimated. In addition, the ability of standard MRI to detect threshold‐level effects was confirmed. These safety thresholds are being investigated to provide guidelines for clinical thermal ablation studies in the brain. MRI‐monitored focused ultrasound heating was delivered to 63 locations in 26 rabbits. Tissue changes were detected in T2‐weighted imaging and T1‐weighted imaging (with and without contrast) and with light microscopy. The probability for tissue damage as a function of the accumulated thermal dose, the peak temperature achieved, the applied acoustic energy, and the peak acoustic power was estimated with probit regression. The discriminative abilities of these parameters were compared using the areas under the receiver operator characteristic (ROC) curves. In MRI, BBB disruption was observed in contrast‐enhanced T1‐weighted imaging shortly after the ultrasound exposures, sometimes accompanied by changes in T2‐weighted imaging. Two days later, changes in T2‐weighted imaging were observed, sometimes accompanied by changes in T1‐weighted imaging. In histology, tissue damage was seen at every location where MRI changes were observed, ranging from small (diameter <1.0 mm) areas of tissue necrosis to severe vascular damage and associated hemorrhagic infarct. In one location, small (diameter: 0.8 mm) damage was not detected in MRI. The thermal dose and peak temperature thresholds were between 12.3–40.1 equivalent min at 43°C and 48.0–50.8°C, respectively, and values of 17.5 equivalent min at 43°C and 48.4°C were estimated to result in tissue damage with 50% probability. Thermal dose and peak temperature were significantly better predictors than the applied acoustic energy and peak acoustic power (P < 0.01). BBB disruption was always accompanied by tissue damage. The temperature information was better than the applied acoustic power or energy for predicting the damage than the ultrasound parameters. MRI was sensitive in detecting threshold‐level damage. Magn Reson Med 51:913–923, 2004. © 2004 Wiley‐Liss, Inc.
Fast, three‐dimensional free‐breathing MR imaging of myocardial infarction: A feasibility study
Authors: Saranathan Manojkumar , Rochitte Carlos E. , Foo Thomas K.F.
Published: April 2004

Imaging delayed hyperenhancement of myocardial infarction is most commonly performed using an inversion recovery (IR) prepared 2D breathhold segmented k‐space gradient echo (FGRE) sequence. Since only one slice is acquired per breathhold in this technique, 12–16 successive breathholds are required for complete anatomical coverage of the heart. This prolongs the overall scan time and may be exhausting for patients. A navigator‐echo gated, free‐breathing, 3D FGRE sequence is proposed that can be used to acquire a single slab covering the entire heart with high spatial resolution. The use of a new variable sampling in time (VAST) acquisition scheme enables the entire 3D volume to be acquired in 1.5–2 min, minimizing artifacts from bulk motion and diaphragmatic drift and contrast variations due to contrast media washout. Magn Reson Med 51:1055–1060, 2004. © 2004 Wiley‐Liss, Inc.
Quantitation of simulated short echo time 1H human brain spectra by LCModel and AMARES
Authors: Kanowski Martin , Kaufmann Jörn , Braun Jürgen , Bernarding Johannes , Tempelmann Claus
Published: April 2004

LCModel and AMARES, two widely used quantitation tools for magnetic resonance spectroscopy (MRS) data, were employed to analyze simulated spectra similar to those typically obtained at short echo times (TEs) in the human brain at 1.5 T. The study focused mainly on the influence of signal‐to‐noise ratios (SNRs) and different linewidths on the accuracy and precision of the quantification results, and their effectiveness in accounting for the broad signal contribution of macromolecules and lipids (often called the baseline in in vivo MRS). When applied in their standard configuration (i.e., fitting a spline as a baseline for LCModel, and weighting the first data points for AMARES), both methods performed comparably but with their own characteristics. LCModel and AMARES quantitation benefited considerably from the incorporation of baseline information into the prior knowledge. However, the more accurate quantitation of the sum of glutamate and glutamine (Glx) favored the use of LCModel. Metabolite‐to‐creatine ratios estimated by LCModel with extended prior knowledge are more accurate than absolute concentrations, and are nearly independent of SNR and line broadening. Magn Reson Med 51:904–912, 2004. © 2004 Wiley‐Liss, Inc.
Robust automated shimming technique using arbitrary mapping acquisition parameters (RASTAMAP)
Authors: Klassen L. Martyn , Menon Ravi S.
Published: April 2004

Quantitative MRI techniques as well as methods such as blood oxygen level‐dependent (BOLD) imaging and in vivo spectroscopy require stringent optimization of magnetic field homogeneity, particularly when using high main magnetic fields. Automated shimming approaches require a method of measuring the main magnetic field, B0, followed by adjusting the currents in resistive shim coils to maximize homogeneity. A robust automated shimming technique using arbitrary mapping acquisition parameters (RASTAMAP) using a 3D multiecho gradient echo sequence that measures B0 with high precision was developed. Inherent compensation and postprocessing methods enable removal of artifacts due to hardware timing errors, gradient propagation delays, gradient amplifier asymmetry, and eddy currents. This allows field maps to be generated for any field of view, bandwidth, resolution, or acquisition orientation without custom tuning of sequence parameters. Field maps of an aqueous phantom show ± 1 Hz variation with altered acquisition orientations and bandwidths. Subsequent fitting of measured shim coil field maps allows calculation of shim currents to produce optimum field homogeneity. Magn Reson Med 51:881–887, 2004. © 2004 Wiley‐Liss, Inc.
Electrical and mechanical behavior of filled elastomers 2: The effect of swelling and temperature
Authors: Busfield J. J. C. , Thomas A. G. , Yamaguchi K.
Published: April 2004

In this work the effect of swelling and temperature on the resistivity of highly carbon black filled elastomers under strain is investigated. This work shows that swelling, even to a modest extent of less than 10%, causes a marked increase in the electrical resistivity. The effect of a linear expansion due to swelling is much more marked than an equivalent linear tensile extension on the electrical resistivity. The increase in electrical resistivity with swelling is also much greater than the increase due to a reduction in the volume fraction of the carbon black alone. The increase in resistivity depends somewhat upon the chemical nature of the swelling agent. There is a relatively small effect of temperature induced volume change on resistivity, contrasting markedly with the large effect of a volume increase due to swelling. These observations suggest that on swelling there is a preferential migration of the solvent to the rubber/filler interfaces. This will push the carbon black aggregates apart and lead to a dramatic increase in the resistivity across the interface. There are also indications that at elevated temperatures the filler/rubber interactions are reduced. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2161–2167, 2004
Carbometallate: Komplexe Anionenverbände [MoC4/26—] in der Kristallstruktur von Pr[MoIIC2]
Authors: Dashjav Enkhtsetseg , Kreiner Guido , Schnelle Walter , Wagner Frank R. , Kniep Rüdiger
Published: April 2004

Zunächst werden Kriterien für die Existenz von Carbometallaten entwickelt und in größerem Rahmen diskutiert. Das Konzept wird auf die neue Verbindung Pr2[MoC2] angewendet. Die Charakterisierung der Verbindung erfolgt über chemische Analysen, Röntgenbeugungsexperimente und metallographische Verfahren. Die Kristallstruktur (tetragonal, P42/mnm, Z = 4, a = 581.29(8) pm, c = 1032.53(14) pm) enthält schichtartig aufgebaute Polyanionen [MoC4/26—], die durch Ecken‐ und Kantenverknüpfung von verzerrten MoC4‐Tetraedern entstehen. Praseodym ist ebenfalls verzerrt tetraedrisch von Kohlenstoff umgeben. Die physikalischen Eigenschaften der ternären Verbindung entsprechen denen eines schlechten Metalls (“bad metal”) mit lokalisierten magnetischen 4f‐Momenten, in Übereinstimmung mit dem Vorliegen von Pr3+‐Spezies. Eine detaillierte Bindungsanalyse mit Hilfe der Elektronen‐Lokalisierungsfunktion ELF und der COHP‐Methode rechtfertigt die Beschreibung der Titelverbindung als Carbomolybdat(II).
Molecular analysis of the interaction between palladin and α‐actinin
Authors: Rönty Mikko , Taivainen Anu , Moza Monica , Otey Carol A. , Carpén Olli
Published: April 2004

Palladin is a novel component of stress fiber dense regions. Antisense and transient overexpression studies have indicated an important role for palladin in the regulation of actin cytoskeleton. Palladin colocalizes and coimmunoprecipitates with α‐actinin, a dense region component, but the molecular details and functional significance of the interaction have not been studied. We show here a direct association between the two proteins and have mapped the binding site within a short sequence of palladin and in the carboxy‐terminal calmodulin domain of α‐actinin. Using transfection‐based targeting assays, we show that palladin is involved in targeting of α‐actinin to specific subcellular foci indicating a functional interplay between the two actin‐associated proteins.
Octreotide Scintigraphy in the Detection of Recurrent Paragangliomas
Authors: Bustillo Andres , Telischi F. F.
Published: April 2004

OBJECTIVE

Conventional follow‐up of surgically and radiotherapy‐treated paragangliomas is usually carried out with physical examinations and either magnetic resonance imaging and/or computed tomography. Up to now, octreotide has been reserved for primary diagnosis, for which it has been shown to be a reliable imaging modality. However, the postsurgical and postradiation changes seen on conventional imaging make the diagnosis of small recurrent lesions difficult. We sought to evaluate the role of octreotide scintigraphy in the detection of recurrent paragangliomas.

STUDY DESIGN

We based this case series on 3 patients who were found to have recurrent paragan‐gliomas after primary surgical resection. All patients underwent octreotide scintigraphy during routine follow‐up.

RESULTS

Three patients were found to have recurrent paragangliomas using octreotide scintigraphy. In one of the patients, conventional imaging (magnetic resonance imaging, computed tomography) failed to detect the recurrence.

CONCLUSION

The octreotide study was able to detect the small recurrences because octreotide binds directly to receptors on the tumor and is not affected by postsurgical or postradiotherapy changes. The intrinsic resolution of most commercially available gamma cameras is about 1 cm, making it quite sensitive to detect small tumors. Although this patient did not have synchronous lesions, octreotide scintigraphy can also aide in the detection of such lesions. (Otolaryngol Head Neck Surg 2004;130:479‐82.)
Facial Nerve Paralysis Secondary to Occult Malignant Neoplasms
Authors: Boahene Derek O. , Olsen Kerry D. , Driscoll Colin , Lewis Jean E. , McDonald Thomas J.
Published: April 2004

OBJECTIVE

This study reviewed patients with unilateral facial paralysis and normal clinical and imaging findings who underwent diagnostic facial nerve exploration.

STUDY DESIGN AND SETTING

Fifteen patients with facial paralysis and normal findings were seen in the Mayo Clinic Department of Otorhinolaryngology.

RESULTS

Eleven patients were misdiagnosed as having Bell palsy or idiopathic paralysis. Progressive facial paralysis with sequential involvement of adjacent facial nerve branches occurred in all 15 patients. Seven patients had a history of regional skin squamous cell carcinoma, 13 patients had surgical exploration to rule out a neoplastic process, and 2 patients had negative exploration. At last follow‐up, 5 patients were alive.

CONCLUSIONS

Patients with facial paralysis and normal clinical and imaging findings should be considered for facial nerve exploration when the patient has a history of pain or regional skin cancer, involvement of other cranial nerves, and prolonged facial paralysis.

SIGNIFICANCE

Occult malignancy of the facial nerve may cause unilateral facial paralysis in patients with normal clinical and imaging findings. (Otolaryngol Head Neck Surg 2004;130:459–65.)
Association of Anterior Glottic Webs with Velocardiofacial Syndrome (Chromosome 22q11.2 Deletion)
Authors: Miyamoto R. Christopher , Cotton Robin T. , Rope Alan F. , Hopkin Robert J. , Cohen Aliza P. , Shott Sally R. , Rutter Michael J.
Published: April 2004

OBJECTIVE

An association between anterior glottic webs and velocardiofacial syndrome (chromosome 22q11.2 deletion) has previously been noted in a number of case reports. Our objective was to determine if the presence of such webs warrants a high index of suspicion for this chromosome deletion.

STUDY DESIGN AND SETTING

This study was carried out in the Division of Pediatric Otolaryngology‐Head and Neck Surgery at Cincinnati Children's Hospital Medical Center. Chromosome 22q11.2 deletion status was determined for all patients endoscopically diagnosed with anterior glottic webs between July 1998 and December 2000. Families of patients who tested positive for the deletion were referred to the Cincinnati Children's Division of Human Genetics for additional evaluation and counseling.

RESULTS

Eleven of 17 patients (65%) with anterior glottic webs were positive for chromosome 22q11.2 deletion. Of these 11 patients, 5 showed subtle clinical manifestations of velocardiofacial syndrome and underwent genetic testing due only to the presence of a web. All 11 patients were diagnosed with velocardiofacial syndrome.

CONCLUSION

We strongly recommend that all patients diagnosed with anterior glottic webs undergo fluorescence in situ hybridization evaluation for this chromosome deletion. (Otolaryngol Head Neck Surg 2004;130:415‐7.)
Flutamide as a Preoperative Treatment in Juvenile Angiofibroma (JA) with Intracranial Invasion: Report of 7 Cases
Authors: Labra Alberto , Chavolla‐Magaña Rogelio , Lopez‐Ugalde Adriana , Alanis‐Calderon Jorge , Huerta‐Delgado Angel
Published: April 2004

OBJECTIVE

To determine the efficacy of flutamide as a tumor reduction factor in patients who have juvenile anglofibroma (JA) with intracranial invasion.

DESIGN

A longitudinal, prospective, experimental, self‐controlled pilot study.

MATERIAL AND METHODS

Seven consecutive patients with JA were enrolled in the study. CT scan with measurements of the tumor was performed before and after the treatment with flutamide, and the results were compared.

RESULTS

The biggest reduction in tumor size was 11.1%. All patients underwent surgical resection, and the bleeding was similar to patients without flutamide. No statistically significant difference was found between the measurements before and after the flutamide administration.

CONCLUSIONS

Despite the fact that there is a report of the efficacy of flutamide in the literature, we did not find advantages in using it in patients with JA. However, and due to the very small number of patients enrolled, we think that more studies are required.
Plasma channels and electron density profiles near the midnight plane in the Venus nightside ionosphere
Authors: Pérez‐de‐Tejada H.
Published: April 2004

Pioneer Venus Orbiter (PVO) data with information on the electron densities in the Venus nightside ionosphere are examined in a study of the plasma channels that extend downstream from the magnetic polar regions. The plasma channels are produced by the solar wind that erodes the polar upper ionosphere and provide a useful interpretation of the ionospheric holes as regions of depleted plasma density that are observed in the nightside hemisphere. The plasma channels can also account for the observed distribution of ionospheric holes in the nightside hemisphere as a function of the solar wind dynamic pressure. Wide plasma channels that result from the enhanced erosion of the polar upper ionosphere under high dynamic pressures lead to the ionospheric holes that are observed far from the midnight plane. Data obtained from the PVO show that in addition to the ionospheric holes there are orbits traced near the midnight plane with measurements that are also related to the plasma channels. In some cases the electron density does not change significantly through the upper ionosphere but exhibits a density plateau that extends from a high‐altitude nightside ionopause crossing to a low‐altitude location where a sharp change in the density is observed near periapsis. In addition, there are PVO passes in which the nightside ionopause detected near the midnight plane is located at very low altitudes, implying that the PVO may have remained within the plasma channels as it approached or moved away from periapsis. Transit through the bottom of the plasma channels can account for the low‐altitude ionopause crossings seen in these orbits and also for the sharp change at the low‐altitude edge of the density plateau measured in orbits that probed near the midnight plane. Unlike PVO passes in which ionospheric holes are detected near the midnight plane, the magnetic field measured in the solar wind during these latter orbits is not oriented near the ecliptic plane, and thus the magnetic polar regions in the Venus ionosphere and the plasma channels that extend behind them are not encountered along the near polar PVO trajectory. In such cases the spacecraft may not move across the plasma channels but remain along their sides as it travels through the nightside ionosphere. The orientation of the magnetic field with respect to the ecliptic plane can thus account for the observation of ionospheric holes or a density plateau in profiles traced near the midnight plane.
Vertical moisture transport above the mixed layer around the mountains in western Sumatra
Authors: Sasaki Taichi , Wu Peiming , Mori Shuichi , Hamada Jun‐Ichi , Tauhid Yudi I. , Yamanaka Manabu D. , Sribimawati Tien , Yoshikane Takao , Kimura Fujio
Published: April 2004

A remarkable increase in moisture frequently occurred in August afternoon radio soundings in 2001 in the layer up to 1000 m above the mixed layer (ML) near the mountains of western Sumatra, Indonesia. This moisture enhancement was also apparent in the monthly mean diurnal cycle. The mixing ratio is not vertically uniform in this layer, suggesting that turbulent mixing cannot be a major mechanism of the vertical moisture transport. A climatological numerical study using a cloud‐resolving model suggests that thermally‐induced upslope winds converge over the mountain summits during daytime, forming a moist air band along the mountain range. Ambient winds above the mountain range then advect the moist air into the surroundings, moisturizing the air above the ML over the leeward terrain. This mechanism is important for producing diurnal mesoscale precipitation systems over a wide area of the Indian Ocean, as documented by previous studies analyzing TRMM and GMS observational data.
Kinetic analysis of ligand-induced autocatalytic reactions
Authors: LIU Jiang-Hong , WANG Zhi-Xin
Published: April 2004

Protein phosphorylation and limited proteolysis are two most common regulatory mechanisms involving the energy-dependent covalent modification of regulatory enzymes. In addition to modifying other proteins, many protein kinases and proteases catalyse automodification reactions (i.e. reactions in which the kinase or zymogen serves as its own substrate), and their activities are frequently regulated by other regulatory ligands. In the present study, a kinetic analysis of autocatalytic reaction modulated by regulatory ligands is presented. On the basis of the kinetic equation, a novel procedure is developed to evaluate the kinetic parameters of the reaction. As an example of an application of this method, the effects of calcium ions on the autoacatalytic activation of trypsinogen by trypsin is re-examined. The results indicate that the binding affinity for Ca2+-bound trypsinogen to trypsin is at least two orders of magnitude higher than that for Ca2+-free trypsinogen, and therefore that the effect of Ca2+ ions on Km* values for trypsinogen is very much greater than that for the model peptides. Based on the experimental results, one possible molecular mechanism has been proposed.
The identification of a reaction site of glutathione mixed-disulphide formation on gammaS-crystallin in human lens
Authors: CRAGHILL Jane , CRONSHAW Andrew D. , HARDING John J.
Published: April 2004

The glutathionylation of human lens proteins was examined by Western-blot analysis with an anti-GSH antibody and scanning. Several different glutathionylated proteins were observed, and a 47 kDa band was of particular interest. This band did not appear after SDS/PAGE under reducing conditions, suggesting that it was a glutathionylated fraction. The 47 kDa band was found principally in the outer part of the lens, the cortex, but not in the lens nucleus where older proteins are present. The 47 kDa component was composed of βB1-, βB2- and γS-crystallin, with the γS-crystallin having glutathione bound at Cys-82 and at Cys-22, Cys-24 or Cys-26. We conclude that when glutathione becomes bound to γS-crystallin, it causes it to bind in turn to the β-crystallin polypeptides to form a dimer.
Cell-cycle-dependent translation of histone mRNAs is the key control point for regulation of histone biosynthesis in Leishmania infantum
Authors: SOTO Manuel , IBORRA Salvador , QUIJADA Luis , FOLGUEIRA Cristina , ALONSO Carlos , REQUENA Jose M.
Published: April 2004

The cell-cycle-dependent expression of the four core histones (H2A, H2B, H3 and H4) has been studied in the protozoan parasite Leishmania infantum. For that purpose, the cell cycle was arrested by incubation of promastigotes with the DNA synthesis inhibitor hydroxyurea, which induced an accumulation of cells stalled in G1 phase. Hydroxyurea release resulted in a semi-synchronous entry into the cell cycle, as determined by flow cytometry. The steady-state levels of histone mRNAs in the G1, S and G2/M phases were found to be constant along the cell cycle. However, the levels of histone synthesis increased when parasites enter the S phase, in agreement with previous results showing that histone synthesis in Leishmania is tightly coupled with DNA replication. In addition, we analysed the distribution of histone mRNAs on polyribosomes at different stages of the cell cycle by separation of cytoplasmic RNAs in sucrose gradients. Remarkably, a drastic change in the polysome profiles of histone mRNAs was observed during the progression from G1 to S phase. Thus, in the S phase, histone mRNAs are present in ribosome-bound fractions, but in the G1 phase, the histone transcripts are exclusively found in the ribosome-free fractions. These results support a regulatory model in which the cell-cycle-regulated synthesis of histones in Leishmania is controlled through a reversible interaction between translational repressors and histone mRNAs.
Bcl2-low-expressing MCF7 cells undergo necrosis rather than apoptosis upon staurosporine treatment
Authors: POLISENO Laura , BIANCHI Laura , CITTI Lorenzo , LIBERATORI Sabrina , MARIANI Laura , SALVETTI Alessandra , EVANGELISTA Monica , BINI Luca , PALLINI Vitaliano , RAINALDI Giuseppe
Published: April 2004

We present a ribozyme-based strategy for studying the effects of Bcl2 down-regulation. The anti-bcl2 hammerhead ribozyme Rz-bcl2 was stably transfected into MCF7 cancer cells and the cleavage of Bcl2 mRNA was demonstrated using a new assay for cleavage product detection, while Western blot analysis showed a concomitant depletion of Bcl2 protein. Rz-bcl2-expressing cells were more sensitive to staurosporine than control cells. Moreover, both molecular and cellular read-outs indicated that staurosporine-induced cell death was necrosis rather than apoptosis in these cells. The study of the effects of Bcl2 down-regulation was extended to the global MCF7 protein expression profile, exploiting a proteomic approach. Two reference electro-pherograms of Rz-bcl2-transfected cells, one with the ribozyme in a catalytically active form and the other with the ribozyme in a catalytically inactive form, were obtained. When comparing the two-dimensional maps, 53 differentially expressed spots were found, four of which were identified by MALDI-TOF (matrix-assisted laser-desorption ionization–time-of-flight) MS as calreticulin, nucleophosmin, phosphoglycerate kinase and pyruvate kinase. How the up-regulation of these proteins might help to explain the modification of Bcl2 activity is discussed.
Muscarinic-receptor-mediated inhibition of insulin-like growth factor-1 receptor-stimulated phosphoinositide 3-kinase signalling in 1321N1 astrocytoma cells
Authors: BATTY Ian H. , FLEMING Ian N. , DOWNES C. Peter
Published: April 2004

In 1321N1 astrocytoma cells, stimulation of the IGF-1 (insulin-like growth factor-1) receptor increased the association of PI3K [phosphoinositide (PI) 3-kinase] activity with IRS-1 (insulin re-ceptor substrate 1), and increased the cellular concentration of PtdIns(3,4,5)P3. Carbachol, acting on M3 muscarinic receptors, inhibited insulin-, but not PDGF (platelet-derived growth factor)-, stimulated responses by ≈50%. The inhibition of IRS-1-associated PI3K activity by carbachol (i) was rapid (<1 min), persistent (≥60 min) and potent (half-maximal concentration ≈1 µM); (ii) was reproduced by stimuli for several phospholipase-C-coupled receptors; (iii) was prevented by the inhibition of protein kinase C, but not by chelation of intracellular Ca2+; and (iv) was not blocked or reproduced by inhibitors or stimuli respectively of mitogen-activated protein kinase, PI3K, protein kinase B or the mammalian target of rapamycin. However, the effects of carbachol were prevented by sodium vanadate, a protein tyrosine phosphatase inhibitor, and were accompanied by reduced insulin-stimulated IRS-1 tyrosine phosphorylation and recruitment of the 85 kDa regulatory subunit of PI3K to IRS-1, but not by reduced IGF-1 receptor kinase activity. The inhibitory effect of carbachol was reproduced by okadaic acid, a protein serine/threonine phosphatase inhibitor, but not by PDGF, yet all three agents stimulated the serine phosphorylation of IRS-1 at residues Ser312, Ser616 and Ser636/639, albeit to different extents. Thus muscarinic receptors may inhibit insulin signalling by promoting IRS-1 tyrosine dephosphorylation and/or by uncoupling IRS-1 from the stimulated IGF-1 receptor by stimulating IRS-1 serine phosphorylation. However, the proportion of IRS-1 molecules phosphorylated at a particular site or the phosphorylation of additional IRS-1 serine residues other than those noted above must be important.
Factors determining the oxygen consumption rate (V.o2) on-kinetics in skeletal muscles
Authors: KORZENIEWSKI Bernard , ZOLADZ Jerzy A.
Published: April 2004

Using a computer model of oxidative phosphorylation developed previously [Korzeniewski and Mazat (1996) Biochem. J. 319, 143–148; Korzeniewski and Zoladz (2001) Biophys. Chem. 92, 17–34], we analyse the effect of several factors on the oxygen-uptake kinetics, especially on the oxygen consumption rate (Vo2) and half-transition time t1/2, at the onset of exercise in skeletal muscles. Computer simulations demonstrate that an increase in the total creatine pool [PCr±Cr] (where Cr stands for creatine and PCr for phosphocreatine) and in glycolytic ATP supply lengthen the half-transition time, whereas increase in mitochondrial content, in parallel activation of ATP supply and ATP usage, in oxygen concentration, in proton leak, in resting energy demand, in resting cytosolic pH and in initial alkalization decrease this parameter. Theoretical studies show that a decrease in the activity of creatine kinase (CK) [displacement of this enzyme from equilibrium during on-transient (rest-to-work transition)] accelerates the first stage of the Vo2 on-transient, but slows down the second stage of this transient. It is also demonstrated that a prior exercise terminated a few minutes before the principal exercise shortens the transition time. Finally, it is shown that at a given ATP demand, and under conditions where CK works near the thermodynamic equilibrium, the half-transition time of Vo2 kinetics is determined by the amount of PCr that has to be transformed into Cr during rest-to-work transition; therefore any factor that diminishes the difference in [PCr] between rest and work at a given energy demand will accelerate the Vo2 on-kinetics. Our conclusions agree with the general idea formulated originally by Easterby [(1981) Biochem. J. 199, 155–161] that changes in metabolite concentrations determine the transition times between different steady states in metabolic systems.
The anti-Mullerian hormone type II receptor: insights into the binding domains recognized by a monoclonal antibody and the natural ligand
Authors: SALHI Imed , CAMBON-ROQUES Sylvie , LAMARRE Isabelle , LAUNE Daniel , MOLINA Franck , PUGNIÈRE Martine , POURQUIER Didier , GUTOWSKI Marian , PICARD Jean-Yves , XAVIER Françoise , PÈLEGRIN André , NAVARRO-TEULON Isabelle
Published: April 2004

Anti-Müllerian hormone (AMH) [also called Müllerian inhibiting substance (MIS)] is a member of the transforming growth factor-β family. AMH and its type II receptor (AMHR-II) are involved in the regression of the Müllerian ducts in the male embryo, and in gonadal functions in the adult. AMH is also known to be a marker of granulosa and Sertoli cell tumours. We selected a high-affinity monoclonal antibody, mAb 12G4, specific for human AMHR-II (hAMHR-II), by FACS analysis, Western blotting and immunohistochemical staining of a hAMHR-II-transfected CHO (Chinese hamster ovary) cell line, normal adult testicular tissue and granulosa cell tumours. Using peptide array screening, we identified the binding sequences of mAb 12G4 and AMH on the receptor. Identification of Asp53 and Ala55 as critical residues in the DRAQVEM minimal epitopic sequence of mAb 12G4 definitively accounted for the lack of cross-reactivity with the murine receptor, in which there is a glycine residue in place of an aspartic acid residue. In a structural model, the AMH-binding interface was mapped to the concave side of hAMHR-II, whereas the mAb 12G4-binding site was located on the convex side. mAb 12G4, the first mAb to be raised against hAMHR-II, therefore has unique properties that could make it a valuable tool for the immunotargeting of tumours expressing this receptor.
Non-invasive evaluation of left ventricular filling pressures in patients with abnormal relaxation
Authors: POERNER Tudor C. , GOEBEL Björn , UNGLAUB Petra , SÜSELBECK Tim , KADEN Jens J. , BORGGREFE Martin , HAASE Karl K.
Published: April 2004

The aim of the present study was to assess the ability of several echocardiographic and TDI (tissue Doppler imaging) parameters to predict an elevated LVEDP (left ventricular end-diastolic pressure) in patients with abnormal relaxation. Eighty-two consecutive patients presenting with an E/A ratio (ratio of early-to-late diastolic peak transmitral velocity) <0.9 scheduled for left heart catheterization underwent echocardiography, including TDI, and measurement of LVEDP using fluid-filled catheters. The difference in duration between PVR (retrograde peak in the pulmonary veins) and A (ΔPVR-A) was calculated from pulsed Doppler recordings. VP (propagation velocity of the early mitral inflow) was determined by colour M-mode. TDI measurements included E´ (early diastolic peak myocardial velocities near the lateral mitral annulus), MVG (the early diastolic transmyocardial velocity gradient of the posterior basal wall) and the PRT (peak relaxation time), determined as the time interval between aortic valve closure and peak E´. Fifty-six patients presented with LVEDP values <15 mmHg, whereas an LVEDP >15 mmHg was found in 26 patients. The index ΔPVR-A showed a significant linear correlation with LVEDP (r=0.7, P<0.001) and provided the highest predictive accuracy for the identification of LVEDP >15 mmHg [AUC (area under receiver operating characteristic curve)=0.83], followed by PRT (AUC=0.67), whereas other TDI-derived parameters failed to reach significance. In conclusion, ΔPVR-A enabled the most accurate non-invasive estimation of LVEDP. A prolonged peak relaxation time was the only TDI-derived index that differed significantly between patient groups.
N-terminal pro-C-type natriuretic peptide, but not C-type natriuretic peptide, is greatly elevated in the fetal circulation
Authors: PRICKETT Timothy C. R. , KAAJA Risto J. , Gary NICHOLLS M. , ESPINER Eric A. , Mark RICHARDS A. , YANDLE Timothy G.
Published: April 2004

We have identified recently a new peptide, NT-proCNP(1–50) (N-terminal pro-C-type natriuretic peptide), in the circulation of humans and sheep. A previous report of an elevated fetal–maternal gradient in immunoreactive CNP raised the possibility that processing and metabolism of proCNP may differ in maternal and fetal tissues. We therefore collected matching peripheral maternal and umbilical cord plasma samples at delivery from women with normotensive and pre-eclamptic pregnancies to investigate the presence and concentrations of CNP and NT-proCNP using HPLC and RIA. Plasma concentrations of NT-proCNP in normotensive umbilical cord plasma were 10-fold higher than maternal venous levels (246±17 compared with 24.3±1.8 pmol/l; P<0.001) and much higher than corresponding levels of CNP (3.6±0.4 compared with 1.8±0.3 pmol/l in the fetal and maternal plasma respectively; P<0.001). Although there was no significant difference between normotensive and pre-eclamptic plasma CNP concentrations in either maternal or umbilical cord blood, NT-proCNP showed a significant statistical interaction (F=5.8, P=0.025) between the source (maternal or fetal) and gestational group (normotensive or pre-eclamptic). Maternal NT-proCNP levels were raised in the pre-eclampsia group, whereas the converse was observed in umbilical cord blood. In conclusion, the greatly elevated ratio of NT-proCNP/CNP in fetal compared with maternal plasma suggests that synthesis, as well as clearance, of CNP (but not NT-proCNP clearance) are markedly increased in fetal tissues.
Thrombospondin-4 A387P polymorphism is not associated with coronary artery disease and myocardial infarction in the Chinese Han population
Authors: ZHOU Xiaoyang , HUANG Jianfeng , CHEN Jianhong , ZHAO Jiangong , YANG Wenjie , WANG Xiaoling , GU Dongfeng
Published: April 2004

Recently, conflicting data have been reported regarding the possible contribution of the TSP-4 (thrombospondin-4) A387P polymorphism to CAD (coronary artery disease) or MI (myocardial infarction). To investigate a possible association between the A387P polymorphism and CAD or MI in the Chinese Han population, we conducted a case-controlled study including 817 patients with angiographically verified CAD or those who survived an acute MI and 847 control subjects. The TSP-4 A387P polymorphism was determined by PCR and PCR-RFLP (restriction-fragment-length polymorphism) analysis. The prevalence of the 387P allele was 3.8% in the healthy controls, which was less frequent than those in Western populations (19.6–23.2%). No association of the A387P polymorphism with an altered risk of CAD, MI or premature MI was found in our present study (CG+CC compared with GG, PCAD=0.51, PMI=0.13, PPremature MI=0.17 respectively). We concluded that a relationship between the TSP-4 A387P polymorphism and CAD or MI was unlikely in our population. Additional investigations should be performed in populations at different risk of coronary events in order to elucidate further the possible contribution of this polymorphism to cardiovascular disease.
Diet, the endothelium and atherosclerosis
Authors: HINGORANI Aroon D.
Published: April 2004

Dietary factors have been implicated in the difference in the risk of cardiovascular disease observed between populations. However, clinical trials and mechanistic studies of dietary modification are difficult to undertake, and the data set on dietary intervention for cardiovascular disease is now much smaller than that for pharmacological interventions. Moreover, the precise mechanism by which dietary modification might alter the risk of cardiovascular disease is uncertain. In this issue of Clinical Science, Ambring and co-workers investigate the effect of a Mediterranean-inspired diet on endothelial function and lipid fractions.
Precursors to pre-eclampsia: are there markers in the fetal circulation?
Authors: HENNESSY Annemarie
Published: April 2004

One of the fundamental issues in pre-eclampsia (hypertension in pregnancy) research is to find serum proteins that can act as markers of disease predisposition, remote disease onset, imminent disease onset or disease activity at the height of its destructive powers. We make assumptions, not infrequently, that positive findings at the time of delivery reflect early changes in the maternal and fetal circulations. Very little has been defined in terms of fetal circulation, as it is, by and large, deemed to be harder to access and less likely to lend itself to useful non-invasive diagnostic tests in early pregnancy. The study published in this issue of Clinical Science by Prickett et al. shows that there is a differential expression of the precursor molecule of CNP (C-type natriuretic peptide), N-terminal proCNP, in pre-eclampsia. At term, pre-eclamptic umbilical cord plasma concentrations are decreased relative to normal pregnancy, possibly reflecting a decrease in placental production. At the same time maternal levels are increased relative to normal pregnancies and this possibly reflects an increase in myometrial/endovascular production. There is no doubt that the predominant actions of these hormones are local and whether plasma levels are a true reflection of dynamic changes in local production and effect is yet to be seen. This study represents a promising start in identifying large stable molecules which could be markers for pre-eclampsia. This study has relatively small numbers of patients and work still needs to be done to determine the utility of umbilical cord levels in early phases of the disease. Whether serum levels of N-terminal proCNP can provide an accurate reflection of normal or pathological maternal uterine adaptation to pregnancy remains a question worth evaluating.
20 μm cutoff heterojunction interfacial work function internal photoemission detectors
Authors: Matsik S. G. , Rinzan M. B. M. , Esaev D. G. , Perera A. G. U. , Liu H. C. , Buchanan M.
Published: April 2004

Results are reported on Heterojunction Interfacial Workfunction Internal Photoemission (HEIWIP) detectors designed for operation up to 20 μm. The peak response of 100 mA/W at 12.5 μm with a D* of 2×1011 Jones was observed with a cutoff wavelength of ∼20 μm. The BLIP temperature for the devices was 40 K at 1.5 V bias. While the peak response remained almost constant (∼95 mA/W) up to 40 K, the D* reduced to 5×109 Jones due to the increased dark current. The response increased with doping while the dark current did not change significantly. Hence, higher responsivity and D* can be expected for designs with higher doping. Designs utilizing increased reflection from the bottom contact are suggested to improve the resonant cavity enhancement for optimizing the detectors, which should lead to higher D* and BLIP temperature.
Optical attenuation signatures of Bacillus subtillis in the THz region
Authors: Brown E. R. , Bjarnason J. E. , Chan T. L. J. , Lee A. W. M. , Celis M. A.
Published: April 2004

This letter reports the use of a photomixing sweep oscillator to characterize samples of B. subtillis spores at room temperature between 200 and 1200 GHz. Dilute (10% by mass) and concentrated samples were tested, the former using fine-grained polyethylene powder as a low-loss dielectric matrix. The dilute sample displays many weak transmission undulations, but the three centered at 418, 1037 and 253 GHz were strong enough to remain after normalization. The concentrated sample displays a much stronger broadband attenuation, precluding accurate measurements above ∼500 GHz. Two broad signatures remain between 250 and 290 GHz, and between 410 and 440 GHz, respectively. The results suggest that single-bioparticle electromagnetic resonance, perhaps from surface phonons, occurs in the dilute sample but is smeared in the concentrated sample.
High frequency oscillation in photonic crystal nanolasers
Authors: Yoshie Tomoyuki , Lončar Marko , Scherer Axel , Qiu Yueming
Published: April 2004

We observed modulated oscillations in lasers of up to 130 GHz by conducting frequency domain measurements on photonic crystal lasers with built-in saturable absorbers. This is an example of how the small volumes of photonic crystal lasers lead to increases in the internal modulation frequencies and enables dramatic improvements of the laser modulation rate.
Sb-mediated growth of Si-doped AlGaAs by molecular-beam epitaxy
Authors: Sadofyev Yu. G. , Johnson S. R. , Chaparro S. A. , Cao Y. , Ding D. , Wang J.-B. , Franzreb K. , Zhang Y.-H.
Published: April 2004

The Sb-mediated growth of Al0.65Ga0.35As is studied for Sb/III flux ratios from 0 to 2% and growth temperatures from 580 to 720 °C. The electrical properties and surface morphology are found to depend strongly on both the growth temperature and the Sb flux. As an isoelectronic dopant, Sb improves the conductivity of n-Al0.65Ga0.35As with the highest conductivities occurring at the highest growth temperatures. As a surfactant, Sb improves the surface morphology at all growth temperatures, with the most dramatic improvement occurring at 670 °C. The smoothest surface (0.2 nm rms roughness) was obtained at 700 °C using a Sb/III flux ratio of 0.02. Furthermore, we have demonstrated that the use of Sb during the molecular-beam-epitaxy growth of AlGaAs effectively eliminates the “forbidden temperature gap.”
Effect of a photonic band gap on scattering from waveguide disorder
Authors: Povinelli M. L. , Johnson Steven G. , Lidorikis Elefterios , Joannopoulos J. D. , Soljačić Marin
Published: April 2004

We derive a general, analytical, coupled-mode theory for disorder-induced scattering in periodic systems that shows that in the experimentally relevant limit of weak disorder, the reflection in a photonic-crystal waveguide is just as low as in a comparable index-guided waveguide. Moreover, since the photonic band gap also blocks radiative loss, the total scattering loss is reduced, and the total transmission is higher. These general results are verified by direct numerical simulations in an example system.