bluuebunny/crossref_metadata_2025 huggingface dataset:
Bryozoan-rich layers in surficial Labrador Slope sediments, eastern Canadian Arctic
Authors: Thomas F C , Hardy I A , Rashid H
Published: May 2003

Layers rich in remains of a shallow-water bryozoan species, Idmidronea atlantica, have been found in Quaternary sediments in a piston core taken from 1085 m water depth in the Labrador Sea (59.700270°N, 60.238370°W), tens of kilometres from the nearest possible source. These layers occur anomalously in pelagichemipelagic muds with abundant planktic and deep-water benthic foraminifera, and are thus not in sediments attributable to mud turbidite or debris flows. The bryozoan remains appear to be most common in intervals just below Heinrich events H1 and H2 (~14 500 and ~20 600 14C years BP, respectively). Two possible ice-related transport mechanisms are suggested to have been involved in the deposition of the bryozoan fragments. The first method involved the scouring action of loose pack ice and (or) bergs dislodging and mobilizing attached bryozoans in shallow water, where they could be subsequently entrained in currents and transported to deeper water. The second method may have occurred when attached colonies of these animals were frozen in place as winter ice formed in shallow water, to be carried out to deeper conditions while still encased in loose floes the subsequent springsummer.
THE GRADIENT OF THE BARRIERS AFFECTS THE RESONANT ENERGY
Authors: OHMUKAI MASATO
Published: May 2003

Double barrier structures with a gradient have been studied by numerical calculations of transmission coefficient following a transfer matrix method. As the slope of the barriers becomes steep, the resonant energy is lowered. On the other hand, the full width at half maximum does not depend on the gradient.
PHOTOLUMINESCENCE STUDIES ON RUBY AT 4.2 K
Authors: BHARDWAJ D. M. , DALELA S. , RAO K. V. R. , JAIN D. C.
Published: May 2003

We have made the PL measurements on ruby at room temperature and 4.2 K. The characteristic R1 and R2 lines of chromium in ruby are found to be absent in the spectra recorded at 4.2 K. Instead of these characteristic lines a band centered on 1.6 eV is observed. A possible explanation has been discussed in terms of co-existence of the two electronic states due to presence of Cr3+ and Cr4+ ions in the ruby lattice.
IR STRUCTURAL INVESTIGATION OF Bi2O3 · GeO2 GLASSES CONTAINING MANGANESE IONS
Authors: ARDELEAN I. , TODOR IOANA , PĂŞCUŢĂA P. , BRATU I.
Published: May 2003

Glasses from the x MnO · (100-x)[ Bi2O3 · GeO2 ] system, with 0≤ x ≤ 50 mol%, have been obtained and characterized by IR spectroscopy in order to obtain information about the influence of MnO on the local structure of the Bi 2 O 3 · GeO 2 glass matrix. The presence and the dependence of the structural units BiO 3, BiO 6 and GeO 4 on the MnO content was analyzed.
ELECTRO-OPTIC EFFECT IN A SEMI-PARABOLIC QUANTUM WELL WITH AN APPLIED ELECTRIC FIELD
Authors: ZHANG LI , XIE HONG-JING
Published: May 2003

By using the compact density matrix approach, the electro-optic effect (EOE) in a semi-parabolic quantum well (QW) with an applied electric field has been theoretically investigated. Via a variant of displacement harmonic oscillation, the exact electronic states in the semi-parabolic QW with an applied electric field are obtained. Numerical results on typical GaAs material reveal that the electro-optic effect nearly linearly increases with the increasing of magnitude of the electric field, but it monotonously decreases with the increasing of confining potential frequency of the semi-parabolic QW. The EOE in the model investigated is 102 times larger than that in the symmetric parabolic QW under the same electric field and the same frequency of parabolic confining potential, which is due to the self-asymmetry of the system and the electric field effect.
RECENT DEVELOPMENTS IN NON-MARKOVIAN STOCHASTIC PETRI NETS
Authors: BOBBIO ANDREA , PULIAFITO ANTONIO , TELEK MIKLÓS , TRIVEDI KISHOR S.
Published: May 2003

Analytical modeling plays a crucial role in the analysis and design of computer systems. Stochastic Petri Nets represent a powerful paradigm, widely used for such modeling in the context of dependability, performance and performability. Many structural and stochastic extensions have been proposed in recent years to increase their modeling power, or their capability to handle large systems. This paper reviews recent developments by providing the theoretical background and the possible areas of application. Markovian Petri Nets are first considered together with very well established extensions known as Generalized Stochastic Petri Nets and Stochastic Reward Nets. Key ideas for coping with large state spaces are then discussed. The challenging area of non-Markovian Petri nets is considered, and the related analysis techniques are surveyed together with the detailed elaboration of an example. Finally new models based on Continuous or Fluid Stochastic Petri Nets are briefly discussed.
A COMBINED APPROACH TO TEXT-DEPENDENT SPEAKER IDENTIFICATION: COMPARISON WITH PURE NEURAL NET APPROACHES
Authors: LIANG QIANHUI , ZHU MIAOLIANG
Published: May 2003

A novel approach to automatic speaker identification (ASI) is presented. Most of the present automatic speaker identification systems based on neural networks have no definite mechanisms to compensate for time distortions due to elocution. Such models have less precise information about the intraspeaker measure. The new combined approach uses both distortion-based and discriminant-based methods. The distortion-based and discriminant-based methods are dynamic time warping (DTW) and artificial neural network (ANN) respectively. This paper compares this new classifier with a pure neural net classifier for speaker identification. The performance of the combined classifier surpasses that of a pure ANN classifier for the conditions tested.
NEW GROUNDED-CAPACITOR CURRENT-MODE OSCILLATORS USING SINGLE-OUTPUT CCIIS
Authors: SOLIMAN AHMED M.
Published: May 2003

In this paper five novel minimal-C and grounded-C current-mode oscillators, using single output CCIIs are reported. The proposed oscillators are classified into three classes based on the number of CCIIs used. The oscillator circuits of class I employ two CCII+s, whereas the class II oscillator employs three CCII+s and those of the class III employ four CCII+s. PSpice simulation results demonstrating the performance of the proposed oscillators are included.
REALIZATION OF ANALOG FUZZY LOGIC CONTROL FOR PWM BOOST CONVERTERS
Authors: LEUNG F. H. F. , WONG L. K. , TAM P. K. S. , LAM H. K.
Published: May 2003

Fuzzy logic controllers (FLCs) have been widely used in many applications. However, they are usually implemented digitally by expensive digital signal processors (DSPs), and the performance is restricted by the sampling period. These disadvantages have limited the applications of FLCs to industrial systems such as switch mode power converters. In this paper, an analog FLC implemented by low-cost devices is proposed. Through analog circuitry, features such as membership function shaping, rule inference and defuzzification are realized. The controller is successfully applied to regulate a PWM boost converter with satisfactory performance.
A DSP–FPGA-BASED RECONFIGURABLE COMPUTER
Authors: ROSENDAHL G. K. , MCLEOD R. D. , CARD H. C.
Published: May 2003

In order to exploit architectural advantages associated with specific computations while at the same time having flexibility in those computations, we have designed a reconfigurable parallel machine architecture. A prototype reconfigurable computer has been constructed based on digital signal processing (DSP) chips and field-programmable gate arrays (FPGAs). Communications are based upon a broadcast network that employs FPGA-based message pre-processing and post-processing. Tradeoffs between computational and communication performance are made possible by software reconfiguration of the FPGAs. The system has been successfully tested on several applications in signal processing.
CORRECT DIAGNOSIS OF ALMOST ALL FAULTY UNITS IN A MULTIPROCESSOR SYSTEM
Authors: THULASIRAMAN K. , DAS ANINDYA , HUANG KAIYUAN , AGARWAL VINOD K.
Published: May 2003

In a t/t-diagnosable system, all faulty units can be located to within a set of no more than t units as long as the number of faulty units present does not exceed t. Furthermore, a unique doubtful unit can be identified; in other words, all faulty units, except possibly for one, can be correctly identified in a t/t-diagnosable system. An open question is "Is t/t-diagnosability necessary for correctly identifying all but one faulty unit?" In this paper, we address the above question and provide an answer. We establish necessary and sufficient conditions for correct diagnosis of all except possibly one faulty unit. In addition, we show that the fault-free state is indistinguishable from a faulty state in a t/t-diagnosable system and propose a remedy. These considerations result in the definition and characterization of a new class of systems called t/-1 diagnosable systems.
HANDWRITTEN CHINESE CHARACTER RECOGNITION WITH DIRECTIONAL DECOMPOSITION CELLULAR FEATURES
Authors: JIN LIANWEN , WEI GANG
Published: May 2003

A new feature extraction approach based on elastic meshing and directional decomposition techniques for handwritten Chinese character recognition (HCCR) is proposed in this letter. It is found that decomposing a Chinese character into horizontal, vertical stroke, left slant and right slant directional sub-patterns is very helpful for feature extraction and recognition. Three kinds of decomposition methods are proposed. A minimum distance classifier is trained by 3755 categories of characters using the new features. Testing on a total of 37,550 untrained handwritten samples produces the recognition rate of 92.36%, showing the effectiveness of the proposed approach.
VLSI FLOATING RESISTORS FOR NEURAL TYPE CELL ARRAYS
Authors: SELLAMI L. , SINGH S. K. , NEWCOMB R. W. , RASMUSSEN A. , ZAGHLOUL M. E.
Published: May 2003

Two novel CMOS circuit designs implementing floating resistors are introduced, using the structure of a two-transistor CMOS bilateral linear resistor in the first configuration and two two-transistor CMOS bilateral linear resistors and cascode current mirrors in the second configuration. Linearity is achieved through nonlinearity cancellation via current mirrors over an applied range of ±5V. PSpice simulation results using parameters of MOSIS transistors are presented to verify the theory. These floating resistors can be used for coupling weights in VLSI neural-type cell arrays.
ANALOG DENDRO-DENDRITIC ARRAYS WITH DIGITAL ON-CHIP LEARNING
Authors: SALAM F. M. , WANG Y. , ERTEN G.
Published: May 2003

A design of arrays of CMOS analog Dendro-dendritic Artificial Neural Network (DANN) chips with on-chip digital learning is described. The building blocks, namely, the neuron unit and the adaptive synapse, are employed to construct several architectures. One design comprises a reconfigurable fully-connected array chip integrating 50-neurons. A second array chip design integrates (9×9=81) neuron units and 825 locally-connected reconfigurable weights. In all cases, a connection is realized as a single (nonlinear) transistor with adaptive digital circuitry. The chip is designed and fabricated in 6.8 mm× 4.6 mm chip size using 2 μm CMOS technology. As an example of an application of the fabricated dendro-dendritic neural chips, real-time experiments are described in which the chips are used as a parallel digital coprocessor to demonstrate their applicability as pattern associators. These experiments entail learning an arbitrary binary image in about 10 ns with guaranteed learning capability. The stored image can subsequently be retrieved by images distorted by binary-noise in the order of 100 ns. The power dissipation of these chips in steady state is less than 5 mW using 0/5 V power supply.
DIGITAL ARITHMETIC USING ANALOG CELLULAR NEURAL NETWORKS
Authors: SADEGHI-EMAMCHAIE SAEID , JULLIEN G. A. , DIMITROV V. S. , MILLER W. C.
Published: May 2003

We discuss the realization of digital arithmetic using analog arrays in the form of Cellular Neural Networks (CNNs). These networks replace the fast switching nodes of logic gates with slewing nodes using current sources driving into capacitors; this provides both low current spikes and low voltage slewing rates, reducing system noise and cross-talk in low-voltage mixed-signal applications. In this paper we generalize the design methodology using a Symbolic Substitution (SS) technique, and we use a recently developed Double-Base Number System (DBNS) to illustrate our design technique. This choice is predicated on the fact that the DBNS representation is naturally 2-dimensional and excites more degrees of freedom in the design space. Spatial configurations of the recognition/replacement patterns used in SS are defined based on the properties of the DBNS arithmetic operation. The SS recognition phases are implemented by dynamic evaluation of simple conditions defined based on an analysis of the cell dynamic routes. The replacement phases are automatically executed through switching current which force the transition of cell state voltage between logic levels. In effect, we build self-timed logic arrays with all nodes in the system under controlled slew. Simulation results from schematic level designs are provided to demonstrate the effectiveness of the technique.
What Sets the Long-Term Level of Renal Sympathetic Nerve Activity
Authors: Barrett Carolyn J. , Ramchandra Rohit , Guild Sarah-Jane , Lala Aneela , Budgett David M. , Malpas Simon C.
Published: May 2003

Increasing evidence suggests elevated sympathetic outflow may be important in the genesis of hypertension. It is thought that peripheral angiotensin II, in addition to its pressor actions, may act centrally to increase sympathetic nerve activity (SNA). Without direct long-term recordings of SNA, testing the involvement of neural mechanisms in angiotensin II–induced increases in arterial pressure is difficult. Using a novel telemetry-based implantable amplifier, we made continuous recordings of renal SNA (RSNA) before, during, and after 1 week of angiotensin II–based hypertension in rabbits living in their home cages. Angiotensin II infusion (50 ng · kg
−1
· min
−1
) caused a sustained increase in arterial pressure (18±3 mm Hg). There was a sustained decrease in RSNA from 18±2 normalized units (n.u.) before angiotensin II to 8±2 n.u. on day 2 and 9±2 n.u. on day 7 of the angiotensin II infusion (
P
<0.01) before recovering to 17±2 n.u. after ceasing angiotensin II. Analysis of the baroreflex response showed that although angiotensin II–induced hypertension led to resetting of the relationship between mean arterial pressure (MAP) and heart rate, there was no evidence of resetting of the MAP-RSNA relationship. We propose that the lack of resetting of the MAP-RSNA curve, with the resting point lying near the lower plateau, suggests the sustained decrease in RSNA during angiotensin II is baroreflex mediated. These results suggest that baroreflex control of RSNA and thus renal function is likely to play a significant role in the control of arterial pressure not only in the short term but also in the long term.
Functional Cooperation Between Smad Proteins and Activator Protein-1 Regulates Transforming Growth Factor-β–Mediated Induction of Endothelin-1 Expression
Authors: Rodríguez-Pascual Fernando , Redondo-Horcajo Mariano , Lamas Santiago
Published: May 2003

Endothelin-1 (ET-1) is a 21–amino-acid potent vasoconstrictor peptide that is mainly produced by vascular endothelial cells. Expression of the ET-1 gene is subject to complex regulation by numerous factors, among which transforming growth factor-β (TGF-β) is one of the most important. It has been widely documented that TGF-β increases ET-1 mRNA and peptide levels. We have explored the mechanism by which TGF-β upregulates ET-1 expression in endothelial cells. Transcriptional activation of the ET-1 promoter accounted for the TGF-β–induced increase in ET-1 mRNA levels. We have identified within the ET-1 promoter two DNA elements indispensable for TGF-β–mediated induction of ET-1: an activator protein-1 (AP-1) site at −108/−102, known to be important for constitutive and induced expression, and a novel regulatory sequence located at −193/−171, which constitutes a specific binding site for Smad transcription factors. Mutation of both elements abolished TGF-β responsiveness. Binding of Smad3/Smad4 and c-Jun to their corresponding DNA elements was evidenced by electrophoretic mobility shift assays. Furthermore, the coactivator CREB-binding protein (CBP)/p300 was found to play an essential role in the induction of the gene. The simultaneous requirement for two distinct and independent DNA elements suggests that Smads and activator protein-1 functionally cooperate through CBP/p300 to mediate TGF-β–induced transcriptional activation of the ET-1 gene.
Effect of Steady Versus Oscillating Flow on Porcine Coronary Arterioles
Authors: Sorop Oana , Spaan Jos A.E. , Sweeney Terrence E. , VanBavel Ed
Published: May 2003

Coronary blood vessels are compressed by the contracting myocardium. This leads to oscillations in flow in especially the subendocardium. We examined the effects of steady and oscillating flow on isolated, cannulated subendocardial and subepicardial porcine arterioles. Steady flow–induced dilation in both vessel types, up to 12.9±0.8% of the passive diameter in subendocardials and 9.6±1.4% in subepicardials at 40 dyne/cm
2
. Dilation was completely abolished after treatment with 10 μmol/L L-NNA. Sinusoidal modulation of steady flow at 1.5 Hz and 50% to 200% amplitude did not affect dilation. Oscillating flow without a net forward component with peak-peak shear values up to 100 dyne/cm
2
caused no dilation at all in these vessels. However, in the presence of 100 U/mL superoxide dismutase (SOD), oscillating flow induced dilation up to 19.5±2.3% in subendocardial vessels and 11.5±4.3% in subepicardials. LNNA (10 μmol/L) blocked this dilation by approximately 50%. SOD did not affect the magnitude of steady flow-induced dilation, but the response time after onset of steady flow shortened from 23.4±1.5 to 14.3±2.1 seconds. Diphenyleneiodinium, an inhibitor of NAD(P)H oxidase, uncovered dilation to oscillating flow in subendocardial vessels up to 9.5±1.6%. Flow causes production of both NO and O
2
−
. During steady flow, the bioavailability of NO is sufficient to cause vasodilation. During oscillating flow, NO is quenched by the O
2
−
, suppressing vasodilation. Considering the pulsatile nature of subendocardial flow and the vulnerability of this layer, pharmacological manipulation of the balance between NO and O
2
−
may improve subendocardial perfusion.
Upregulation of CD40-CD40 Ligand (CD154) in Patients With Acute Cerebral Ischemia
Authors: Garlichs C.D. , Kozina S. , Fateh-Moghadam S. , Tomandl B. , Stumpf C. , Eskafi S. , Raaz D. , Schmeißer A. , Yilmaz A. , Ludwig J. , Neundörfer B. , Daniel W.G.
Published: May 2003

Background and Purpose—

Inflammation and hypercoagulability contribute to the development of acute cerebral ischemia. Both can be mediated by the CD40 system. This study investigated whether the CD40 system and related mediators are upregulated in patients with transient ischemic attack (TIA) or stroke.

Methods—

Seventeen patients with TIA, 60 patients with complete stroke, and 15 control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 on monocytes during and 3 months after acute cerebral ischemia by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated.

Results—

Our main findings are as follows: (1) patients with acute cerebral ischemia showed a significant increase of CD154 on platelets and CD40 on monocytes compared with controls; (2) plasma levels of soluble CD154 were significantly higher in these patients; (3) these patients had significantly higher numbers of prothrombotic platelet-monocyte aggregates; (4) the chemoattractant MCP-1 was significantly elevated in cerebral ischemia; and (5) at 3 months’ follow-up, upregulation of CD154 still persisted in patients with previous acute cerebral ischemia.

Conclusions—

Patients with acute cerebral ischemia show upregulation of the CD40 system, which might contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.
Major Risk Factors for Aneurysmal Subarachnoid Hemorrhage in the Young Are Modifiable
Authors: Broderick Joseph P. , Viscoli Catherine M. , Brott Thomas , Kernan Walter N. , Brass Lawrence M. , Feldmann Edward , Morgenstern Lewis B. , Wilterdink Janet Lee , Horwitz Ralph I.
Published: May 2003

Background and Purpose—

To identify risk factors for subarachnoid hemorrhage (SAH) and intracerebral hemorrhage, we designed a case-control study of men and women 18 to 49 years of age (the Hemorrhagic Stroke Project [HSP]). This report focuses on SAH.

Methods—

Patients were recruited from 44 hospitals in the United States. Cases with SAH must have had a ruptured aneurysm documented by angiography or surgery. Two controls, identified by random digit dialing and matched to each patient for age, sex, race, and telephone exchange, were sought for each case subject.

Results—

Between 1994 and 1999, 425 patients with SAH were enrolled in HSP, and 312 cases met the criteria for aneurysmal SAH. The present analyses also included 618 matched controls. Of the 312 cases, 66% were current cigarette smokers compared with 30% of controls (adjusted odds ratio [OR], 3.73; 95% CI, 2.67 to 5.21). Cocaine use within the previous 3-day period was reported by 3% of cases and no controls (bivariate exact OR, 24.97; 95% exact CI, 3.95 to ∞; adjusted estimate not calculable). Other independent risk factors in the multivariable model included hypertension (adjusted OR, 2.21; 95% CI, 1.48 to 3.29), low body mass index (OR, 1.59; 95% CI, 1.08 to 2.35), primary family history of hemorrhagic stroke (OR, 3.83; 95% CI, 1.73 to 8.46), caffeine in pharmaceutical products (OR, 2.48; 95% CI, 1.19 to 5.20), lower educational achievement (OR, 2.36; 95% CI, 1.44 to 3.87), and nicotine in pharmaceutical products (adjusted estimate not calculable).

Conclusions—

Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use). The association of caffeine and nicotine in pharmaceutical products and aneurysmal SAH warrants further study.
Inhibition of NF-κB by a TAT-NEMO–binding domain peptide accelerates constitutive apoptosis and abrogates LPS-delayed neutrophil apoptosis
Authors: Choi Mira , Rolle Susanne , Wellner Maren , Cardoso M. Cristina , Scheidereit Claus , Luft Friedrich C. , Kettritz Ralph
Published: May 2003

Delivery of biologically active peptides into human polymorphonuclear neutrophils (PMNs) has implications for studying cellular functions and may be therapeutically relevant. The transcription factor nuclear factor-κB (NF-κB) regulates the expression of multiple genes controlling inflammation, proliferation, and cell survival. PMNs play a crucial role in first-line defense. Targeting NF-κB in these cells may promote apoptosis and therefore facilitate resolution of inflammation. We used an 11-amino acid sequence NEMO-binding domain (NBD) that selectively inhibits the IKKγ (NEMO)/IKKβ interaction, preventing NF-κB activation. An HIV-TAT sequence served as a highly effective transducing shuttle. We show that lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), and dexamethasone (DEX) significantly reduced apoptosis after 20 hours. LPS, but not GM-CSF or DEX, activated NF-κB as shown by IκBα degradation, NF-κB DNA binding, and transcriptional activity. The TAT-NBD blocked LPS-induced NF-κB activation and NF-κB–dependent gene expression. TAT-NBD accelerated constitutive PMN apoptosis dose dependently and abrogated LPS-delayed apoptosis. These results provide a proof of principle for peptide delivery by TAT-derived protein transduction domains to specifically inhibit NF-κB activity in PMNs. This strategy may help in controlling various cellular functions even in short-lived, transfection-resistant primary human cells.
Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses
Authors: Amrolia Persis J. , Muccioli-Casadei Giada , Yvon Eric , Huls Helen , Sili Uluhan , Wieder Eric D. , Bollard Catherine , Michalek Jaroslav , Ghetie Victor , Heslop Helen E. , Molldrem Jeffrey J. , Rooney Cliona M. , Schlinder John , Vitetta Ellen , Brenner Malcolm K.
Published: May 2003

Poor immune reconstitution after haploidentical stem cell transplantation results in a high mortality from viral infections and relapse. One approach to overcome this problem is to selectively deplete the graft of alloreactive cells using an immunotoxin directed against the activation marker CD25. However, the degree of depletion of alloreactive cells is variable following stimulation with recipient peripheral blood mononuclear cells (PBMCs), and this can result in graft versus host disease (GVHD). We have refined this approach using recipient Epstein-Barr virus (EBV)–transformed lymphoblastoid cell lines (LCLs) as stimulators to activate donor alloreactive T cells. Our studies demonstrate that allodepletion with an anti-CD25 immunotoxin following stimulation with HLA-mismatched host LCLs more consistently depleted in vitro alloreactivity than stimulation with host PBMCs, as assessed in primary mixed lymphocyte reactions (MLRs). Allodepletion using this approach specifically abrogates cytotoxic T-cell responses against host LCLs. In interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assays, antiviral responses to adenovirus and cytomegalovirus (CMV) were preserved following allodepletion. Likewise, using HLA-A2–pp65 tetramers, we have shown that the frequency of CMV-specific T cells is unaffected by allodepletion. Moreover, the donor anti-EBV response is partially retained by recognition of EBV antigens through the nonshared haplotype. Finally, we studied whether allodepletion affects the response to candidate tumor antigens in myeloid malignancies. Using HLA-A2–PR1 tetramer analysis, we found that the frequency of T cells recognizing the PR1 epitope of proteinase 3 was not significantly different in allodepleted and unmanipulated PBMCs from patients with chronic myeloid leukemia (CML) undergoing transplantation. Based on these data, we have embarked on a phase 1 clinical trial of addback of allo-LCL–depleted donor T cells in the haplo-identical setting.
Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation
Authors: Laport Ginna G. , Levine Bruce L. , Stadtmauer Edward A. , Schuster Stephen J. , Luger Selina M. , Grupp Stephan , Bunin Nancy , Strobl Frank J. , Cotte Julio , Zheng Zhaohui , Gregson Brian , Rivers Patricia , Vonderheide Robert H. , Liebowitz David N. , Porter David L. , June Carl H.
Published: May 2003

We explored the feasibility and toxicity of administering escalating doses of anti-CD3/CD28 ex vivo costimulated T cells as a therapeutic adjunct for patients with relapsed, refractory, or chemotherapy-resistant, aggressive non-Hodgkin lymphoma (NHL) following high-dose chemotherapy and CD34+-selected hematopoietic cell transplantation (HCT). Sixteen patients had infusions on day 14 after HCT of autologous T cells that had been stimulated using beads coated with anti-CD3 and anti-CD28 monoclonal antibodies. At baseline, the subjects had severe quantitative and functional T-cell impairments. The culture procedure partially reversed impaired cytokine responsiveness in T cells in vitro and in vivo. Transient dose-dependent infusion toxicities were observed. There was a rapid reconstitution of lymphocytes; however, there were persistent defects in CD4 T cells. Most interestingly, 5 patients had a delayed lymphocytosis between day 30 and day 120 after HCT. Maximal clinical responses included 5 patients with a complete response (CR), 7 patients with a partial response (PR), and 4 patients with stable disease. At a median follow-up of 33 months (range, 26-60 months), 5 patients are alive with stable or relapsed disease and 3 patients remain in CR. In conclusion, this phase 1 trial demonstrates that adoptive transfer of autologous costimulated T cells (1) is feasible in heavily pretreated patients with advanced NHL, (2) is associated with a rapid recovery of lymphocyte counts, (3) reverses cytokine activation deficits in vitro, and (4) is associated with delayed lymphocytosis in a subset of patients.
Imatinib mesylate inhibits autonomous erythropoiesis in patients with polycythemia vera in vitro
Authors: Oehler Leopold , Jaeger Eva , Eser Alexander , Sillaber Christian , Gisslinger Heinz , Geissler Klaus
Published: May 2003

The overproduction of red blood cells in patients with polycythemia vera (PV) is reflected in vitro by the formation of erythroid burst-forming units (BFU-Es) in the absence of exogenous erythropoietin. In contrast to other myeloproliferative disorders, the molecular mechanism of PV is unknown and no specific chromosomal abnormality has been described. We speculated that imatinib mesylate may reverse the pathological overproduction of red cells by inhibition of autonomous erythropoiesis. In the present study, imatinib mesylate was found to either block or strongly inhibit autonomous BFU-E formation in vitro in all patients tested. Moreover, autonomous BFU-E growth was also markedly reduced by exposure of PV cells to imatinib mesylate prior to cultivation in semisolid medium. The profound effect of imatinib mesylate on autonomous erythropoiesis suggests the involvement of an as yet unidentified kinase in the pathogenesis of PV and should provide the rationale for a forthcoming clinical trial.
α3β1-integrin regulates hair follicle but not interfollicular morphogenesis in adult epidermis
Authors: Conti Francesco J. A. , Rudling Robert J. , Robson Alistair , Hodivala-Dilke Kairbaan M.
Published: May 2003

α3β1-integrin is abundantly expressed in the epidermis, and in mice, ablation of the α3 gene results in embryonic defects and perinatal lethality. To determine the role of α3-integrin in adult skin development, we grafted skin from newborn α3-integrin-deficient mice on to ICRF nu/nu recipients. We report that adult α3-integrin-deficient skin has severe abnormalities restricted to hair follicle morphology, which include stunted hair follicle growth, increased hair follicle fragility,aberrant pigment accumulation and formation of hair follicle clusters. These abnormalities are caused by a combination of defects in: (1) keratinocyte cytoskeletal organisation, (2) outer root sheath architecture and (3)integrity of the lamina densa. Our results indicate that α3β1 is not essential for adult interfollicular epidermal differentiation, but it is required to direct several processes important in hair follicle maintenance and morphogenesis.
Regulation of early endocytic vesicle motility and fission in a reconstituted system
Authors: Bananis Eustratios , Murray John W. , Stockert Richard J. , Satir Peter , Wolkoff Allan W.
Published: May 2003

We previously established conditions to reconstitute kinesin-dependent early endocytic vesicle motility and fission on microtubules in vitro. The present study examined the question whether motility and fission are regulated in this system. Screening for proteins by immunofluorescence microscopy revealed that the small G protein, Rab4, was associated with 80% of hepatocyte-derived early endocytic vesicles that contain the ligand asialoorosomucoid (ASOR). By contrast, other markers for early endocytic vesicles including clathrin, Rab5 and EEA1 were present in the preparation but did not colocalize with the ASOR vesicles. Guanine nucleotides exchanged into the Rab4 present on the vesicles as shown by solubilization of Rab4 by Rab-GDI; solubilization was inhibited by incubation with GTP-γ-S and promoted by GDP. Pre-incubation of vesicles with GDP increased the number of vesicles moving on microtubules and markedly increased vesicle fission. This increase in motility from GDP was shown to be towards the minus end of microtubules, possibly through activation of the minus-end-directed kinesin,KIFC2. Pre-incubation of vesicles with GTP-γ-S, by contrast, repressed motility. Addition of exogenous GST-Rab4- GTP-γ-S led to a further repression of motility and fission. Repression was not seen with addition of GST-Rab4-GDP. Treatment of vesicles with Rab4 antibody also repressed motility, and repression was not seen when vesicles were pre-incubated with GDP. Based on these results we hypothesize that endogenous Rab4-GTP suppresses motility of ASOR-containing vesicles in hepatocytes and that conversion of Rab4-GTP to Rab4-GDP serves as a molecular switch that activates minus-end kinesin-based motility, facilitating early endosome fission and consequent receptor-ligand segregation.
Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells
Authors: Santel Ansgar , Frank Stephan , Gaume Brigitte , Herrler Michael , Youle Richard J. , Fuller Margaret T.
Published: May 2003

Mitochondrial fusion may regulate mitochondrial morphogenesis and underlie complementation between mitochondrial genomes in mammalian cells. The nuclear encoded mitochondrial proteins Mfn1 and Mfn2 are human homologues of the only known protein mediators of mitochondrial fusion, the Drosophila Fzo GTPase and Saccharomyces cerevisiae yFzo1p. Although the Mfn1 and Mfn2 genes were broadly expressed, the two genes showed different levels of mRNA expression in different tissues. Two Mfn1 transcripts were detected at similar levels in a variety of human tissues and were dramatically elevated in heart, while Mfn2 mRNA was abundantly expressed in heart and muscle tissue but present only at low levels in many other tissues. Human Mfn1 protein localized to mitochondria and participated in a high molecular weight, detergent extractable protein complex. Forced expression of Mfn1 in cultured cells caused formation of characteristic networks of mitochondria. Introduction of a point mutation in the conserved G1 region of the predicted GTPase domain(Mfn1K88T) dramatically decreased formation of mitochondrial networks upon Mfn1 overexpression, suggesting that network formation required completion of the Mfn1 GTPase cycle. Conversely, a protein variant carrying a point mutation in the G2 motif of the Mfn1 GTPase domain acted as a dominant negative: overexpression of Mfn1T109A resulted in fragmentation of mitochondria. We propose that Mfn1T109A interferes with fusion activity of endogenous Mfn1 protein, possibly by binding necessary cofactors,so to allow unopposed mitochondrial fission. Thus, Mfn1 appears to be a key player in mediating mitochondrial fusion and morphology in mammalian cells.
Specific inhibition of pathological prion protein accumulation by small interfering RNAs
Authors: Daude Nathalie , Marella Mathieu , Chabry Joëlle
Published: May 2003

Development of transmissible spongiform encephalopathies (TSEs)pathogenesis requires the presence of both the normal host prion protein(PrP-sen) and the abnormal pathological proteinase-K resistant isoform(PrP-res). PrP-res forms highly insoluble aggregates, with self-perpetuating properties, by binding and converting PrP-sen molecules into a likeness of themselves. In the present report, we show that small interfering RNA (siRNA)duplexes trigger specific Prnp gene silencing in scrapie-infected neuroblastoma cells. A non-passaged, scrapie-infected culture transfected with siRNA duplexes is depleted of PrP-sen and rapidly loses its PrP-res content. The use of different murine-adapted scrapie strains and host cells did not influence the siRNA-induced gene silencing efficiency. More than 80% of transfected cells were positive for the presence of fluorescein-labeled siRNA duplexes. No cytotoxicity associated with the use of siRNA was observed during the time course of these experiments. Despite a transient abrogation of PrP-res accumulation, our results suggest that the use of siRNA may provide a new and promising therapeutic approach against prion diseases.
Visual resolution of gratings by the compound eye of the bee Apis mellifera
Authors: Horridge G. Adrian
Published: May 2003

Early measurements of the resolution of horizontal versus vertical gratings were confirmed, with a limit near a period of 2.5°, and the resolution is similar when vertical or horizontal gratings are tested separately against grey. Bees were next trained to discriminate from a distance between gratings at 45° versus 135°, with no green contrast, on targets presented in a vertical plane at a fixed distance. As expected, they fail to learn; however, with green contrast but no modulation difference the resolution limit is near 3.5°. With vertical and horizontal gratings with no green contrast they discriminate but do not learn an orientation cue. In order to eliminate the orientation cue altogether, new bees were then trained with alternating vertical and horizontal gratings versus grey, or with a black and white checkerboard versusgrey. Tests of these trained bees with horizontal or with vertical gratings separately against grey again show a resolution down to a period near 2.5°. These results, taken together, show that when edge orientation alone is the cue, the limit of resolution is near 3.5°, but when receptor modulation is the cue, the limit is near 2.5°.
Molecular characterisation of the smooth endoplasmic reticulum Ca2+-ATPase ofPorcellio scaberand its expression in sternal epithelia during the moult cycle
Authors: Hagedorn Monica , Weihrauch Dirk , Towle David W. , Ziegler Andreas
Published: May 2003

The anterior sternal epithelial cells of the terrestrial isopod Porcellio scaber transport large amounts of calcium during the formation and resorption of intermittent calcium carbonate deposits. Recent investigations on epithelia involved in mineralisation processes suggest a role of the smooth endoplasmic reticulum Ca2+-ATPase (SERCA) in transcellular calcium transport. We present the first molecular characterisation of a SERCA within a crustacean mineralising epithelium. We cloned the SERCA from a cDNA library of the anterior sternal epithelium and used in situ hybridisation to compare the expression of the SERCA mRNA between three different moulting stages. The full-length SERCA cDNA has an open reading frame of 3006 nucleotides. The deduced 1002 amino-acid polypeptide has a predicted molecular mass of 109.7 kDa and 87% identity to the SERCA of Procambarus clarkii axial muscle isoform. In situ hybridisation confirmed expression within the anterior sternal epithelium and revealed an increase in SERCA mRNA abundance from the non-transporting, early premoult stage to the calcium transporting, late premoult and intramoult stage. The results support previous indications of a contribution by the smooth endoplasmic reticulum to transcellular calcium transport and suggest a transcriptional regulation of SERCA activity.
Role of the post-hepatic septum on breathing during locomotion inTupinambis merianae(Reptilia: Teiidae)
Authors: Klein Wilfried , Andrade Denis V. , Abe Augusto S. , Perry Steven F.
Published: May 2003

Tupinambis merianae increased minute ventilation by increasing both tidal volume and breathing frequency during sustained locomotion at 0.17 m s-1. Animals in which the post-hepatic septum (PHS) had been surgically removed were not able to increase tidal volume during locomotion. Tegus without PHS compensated, in part, by increasing breathing frequency above the levels observed for tegus with intact PHS, but minute ventilation remained less than in the control animals. The rate of oxygen consumption and the air convection requirement, however, were not significantly different between animals with and without PHS, nor at the tested speeds was endurance affected by the removal of the PHS. These data suggest that the PHS facilitates ventilation by acting as a mechanical barrier, preventing the viscera from moving cranially during physical exertion.
Neurotrophin 4/5 is required for the normal development of the slow muscle fiber phenotype in the rat soleus
Authors: Carrasco Dario I. , English Arthur W.
Published: May 2003

During normal postnatal development, rat soleus (SOL) muscle fibers undergo a dramatic fast-to-slow myosin heavy chain (MyHC) isoform transformation. We exploited this phenomenon to evaluate the role of neurotrophin 4/5 (NT-4/5) in the regulation of muscle fiber phenotype. Intramuscular injections of recombinant NT-4/5 into the SOL muscle of rat neonates significantly accelerated the normal fast-to-slow MyHC isoform transformation. Sequestration of endogenous NT-4/5 with TrkB–IgG prevented this transformation from occurring. Administration of the other TrkB ligand, brain-derived neurotrophic factor (BDNF), did not affect the normal course of the MyHC isoform transformation in this muscle, indicating that the observed effect is NT-4/5 specific. Botulinum toxin blockade of synaptic transmission significantly disrupted the normal fast-to-slow MyHC isoform switch. Because administration of NT-4/5 to paralyzed muscles failed to restore the normal course of this MyHC transformation, we believe that the effect of NT-4/5 is not directly on the muscle fibers but that it probably activates or forms a type of retrograde signal to motoneurons. The developmental upregulation of NT-4/5 mRNA in rat SOL muscle fibers occurred earlier than the upregulation of MyHC I/b mRNA associated with muscle fiber transformation. This timing is consistent with the idea that NT-4/5 is involved in early events that lead to the upregulation of the slow MyHC isoform in this muscle.
The representation of conspecific sounds in the auditory brainstem of teleost fishes
Authors: Wysocki Lidia Eva , Ladich Friedrich
Published: May 2003

Temporal patterns of sounds are thought to be the most important carriers of acoustic information in teleost fishes. In order to investigate how conspecific sounds are processed by the auditory system, auditory brainstem responses (ABRs) elicited by conspecific sounds were recorded in five species of teleosts. In the catfishes Platydoras costatus and Pimelodus pictus, the loach Botia modesta and the labyrinth fish Trichopsis vittata, all of which are hearing specialists, each pulse within the sounds elicited a separate brainwave that closely followed the temporal structure. The ABRs of P. costatus and B. modestaalso represent amplitude patterns of conspecific sounds. By contrast, ABRs of the sunfish Lepomis gibbosus, a hearing non-specialist, consisted of long series of waves that could not be attributed to specific sound pulses. A more detailed analysis, however, indicated that each stimulus pulse contributed to the compound ABR waveform. Spectral analysis of low-pitched drumming sounds of P. pictus and corresponding ABRs showed peaks in the ABR spectra at the harmonics of the sound. Our results indicate that,besides temporal patterns, amplitude fluctuations and the frequency content of sounds can be represented in the auditory system and help the fish to extract important information for acoustic communication.
Increase of internal ion concentration triggers trehalose synthesis associated with cryptobiosis in larvae of Polypedilum vanderplanki
Authors: Watanabe Masahiko , Kikawada Takahiro , Okuda Takashi
Published: May 2003

Larvae of an African chironomid, Polypedilum vanderplanki, which live in temporal rock pools, are completely dehydrated when the pools dry up and undergo anhydrobiosis until the next rain comes. During the dehydration process, larvae accumulate large amounts of trehalose, which provides effective protection against desiccation because of its high capacity for water replacement and vitrification. As the occurrence of rapid trehalose synthesis coincides with loss of body water, changes of osmolarity in the body are thought to be a cue for trehalose synthesis. Indeed, exposure to high salinity triggers rapid and efficient accumulation of trehalose even without desiccation treatment. As this rapid production occurs mainly in high concentrations of salt solutions, we conclude that an increase in internal ion concentration triggers trehalose synthesis associated with cryptobiosis in this species.
Functional characterization of a glutamate/aspartate transporter from the mosquitoAedes aegypti
Authors: Umesh Anita , Cohen Bruce N. , Ross Linda S. , Gill Sarjeet S.
Published: May 2003

Glutamate elicits a variety of effects in insects, including inhibitory and excitatory signals at both neuromuscular junctions and brain. Insect glutamatergic neurotransmission has been studied in great depth especially from the standpoint of the receptor-mediated effects, but the molecular mechanisms involved in the termination of the numerous glutamatergic signals have only recently begun to receive attention. In vertebrates, glutamatergic signals are terminated by Na+/K+-dependent high-affinity excitatory amino acid transporters (EAAT), which have been cloned and characterized extensively. Cloning and characterization of a few insect homologues have followed, but functional information for these homologues is still limited. Here we report a study conducted on a cloned mosquito EAAT homologue isolated from the vector of the dengue virus, Aedes aegypti. The deduced amino acid sequence of the protein, AeaEAAT,exhibits 40–50% identity with mammalian EAATs, and 45–50% identity to other insect EAATs characterized thus far. It transports l-glutamate as well as l- and d-aspartate with high affinity in the micromolar range, and demonstrates a substrate-elicited anion conductance when heterologously expressed in Xenopus laevis oocytes, as found with mammalian homologues. Analysis of the spatial distribution of the protein demonstrates high expression levels in the adult thorax, which is mostly observed in the thoracic ganglia. Together, the work presented here provides a thorough examination of the role played by glutamate transport in Ae. aegypti.
Mechanochemical Synthesis of Fluorine-Doped SrTiO3 and Its Photo-oxidation Properties
Authors: Wang Jinshu , Yin Shu , Zhang Qiwu , Saito Fumio , Sato Tsugio
Published: May 2003

Fluorine-doped SrTiO3 powder was prepared by mechanochemical reaction and its photocatalysis has been studied in this paper. The photocatalytic experimental results show that the photocatalytic activity for nitrogen monoxide oxidation of SrTiO3 can be improved by fluorine doping in both visible light and near ultraviolet light range. The photocatalytic activities of SrTiO3 are ca. two and three times larger than those of pure SrTiO3 under the irradiation of wavelength longer than 510 nm and 400 nm.
Acid-doping to Tropone-containing Conjugated Polymer
Authors: Takagi Koji , Mori Kousuke , Kinoshita Takatoshi , Kunisada Hideo , Yuki Yasuo
Published: May 2003

The acid-doping to the tropone-containing conjugated polymer (TCP) was demonstrated. The color of the chloroform solution of TCP changed from orange to dark red by the addition of trifluoroacetic acid, while no color change was observed in the experiment using the low molecular weight model compound. The fluorescence from TCP was completely quenched with the excess amount of a protic acid. The quasi-reversible protonation-deprotonation cycle was confirmed when triethylamine was dropped into the proton-doped TCP.