bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to “Comment on ‘A simple molecular thermodynamic theory of hydrophobic hydration’ ” [J. Chem. Phys. 119, 10448 (2003)]
Authors: Ashbaugh Henry S. , Truskett Thomas M. , Debenedetti Pablo G.
Published: October 2003

In this response, we present a generalized condition for the observation of entropy convergence behavior for hydrophobic hydration. Applied within the context of our previously developed partition function for aqueous mixtures with nonpolar solutes, it is shown that entropy convergence is observed at a unique temperature when the thermal expansion coefficient of liquid water satisfies specific criterion. Hydrogen-bonding is essential and van der Waals-type fluids never display this phenomenon. Comparing these results to the discussion of Graziano who contends transient hydrogen-bond fluctuations in water dominate entropy convergence, we find that both van der Waals and hydrogen-bonding contributions are significant within the context of our model. In addition, it is pointed out that molecular-level conclusions drawn from a mean-field model should be made with caution.
Improving ab initio infrared spectra of glucose–water complexes by considering explicit intermolecular hydrogen bonds
Authors: Suzuki Teppei , Sota Takayuki
Published: October 2003

In this paper, using density functional theory, we show the effects of explicit intermolecular hydrogen bonds on infrared spectra of glucose–water complexes. The number of explicit water molecules ranges from four to nine, and we approximate the rest of other water molecules as a continuum medium. When eight or nine water molecules are considered explicitly, our computed spectra are in good agreement with the main features of the experimental one. However, in the cases of explicit water molecules less than eight, our computed spectra are not improved successfully. This suggests that in predicting infrared spectrum of glucose in water the effects of explicit water molecules around the glucose molecule are not negligible. We also discuss the numbers of intermolecular hydrogen bonds, spectral differences between α and β anomers, and the main features of normal modes in the 1000–1200 cm−1 region.
A ramp positioner for Besocke type scanning tunneling microscope
Authors: Zhang Zhenfeng
Published: October 2003

A ramp postioner is proposed to eliminate the centrifugal movement of the ramp assembly of Besocke type scanning tunneling microscope. The positioner confines the ramp assembly concentric with the tripod during tip sample coarse approach and is detached from the ramp assembly when tunneling current is obtained. The ramp positioner enables straightforward operation of the microscope.
Optical and electrical properties of in situ-annealed p-type Hg0.7Cd0.3Te epilayers grown on CdTe buffer layers for applications as infrared detectors
Authors: Ryu Y. S. , Heo Y. B. , Song B. S. , Yoon S. J. , Kim Y. J. , Kang T. W. , Kim T. W.
Published: October 2003

Hall-effect, Fourier transform infrared (FTIR) transmission, and photopresponse measurements were performed to investigate the optical and electrical properties of as-grown and in situ-annealed Hg0.7Cd0.3Te epilayers grown on CdTe buffers on GaAs (211) B substrates layers by using molecular-beam epitaxy. Hall-effect measurements showed that as-grown n-Hg0.7Cd0.3Te epilayers were converted to p-Hg0.7Cd0.3Te epilayers due to in situ annealing. The carrier concentration and the mobility as functions of the annealing temperature were determined from the Hall-effect measurements. The FTIR spectra showed that the transmission intensity had increased in comparison to that of the as-grown Hg0.7Cd0.3Te epilayer. Hall-effect measurements showed that n-Hg0.7Cd0.3Te epilayers were converted to p-Hg0.7Cd0.3Te epilayers. The activation energy and the carrier lifetime of the annealed Hg0.7Cd0.3Te epilayer were 0.25 eV and 160 ns, respectively. These results indicate that p-type Hg0.7Cd0.3Te epilayers grown on CdTe buffer layers due to in situ thermal annealing hold promise for potential applications in infrared detector technologies.
Intrinsic limits on electron mobility in dilute nitride semiconductors
Authors: Fahy S. , O’Reilly E. P.
Published: October 2003

A fundamental connection is established between the composition-dependence of the conduction band edge energy and the n-type carrier scattering cross section in the ultradilute limit for semiconductor alloys, imposing general limits on the carrier mobility in such alloys. From the measured nitrogen composition dependence of the bandgap in GaAs1−xNx, the carrier scattering cross section of substitutional nitrogen defects in GaAs is estimated to be 0.3 nm2. Within an independent scattering approximation, the carrier mobility is then estimated to be ∼1000 cm2/V s for a nitrogen atomic concentration of 1%, comparable to the highest measured mobility in high-quality GaInNAs samples at these N concentrations, but substantially higher than that found in many samples. This gives an intrinsic upper bound on the carrier mobility in these materials.
Shell-type micromechanical actuator and resonator
Authors: Zalalutdinov Maxim , Aubin Keith L. , Reichenbach Robert B. , Zehnder Alan T. , Houston Brian , Parpia Jeevak M. , Craighead Harold G.
Published: October 2003

Dome-shaped radio-frequency micromechanical resonators were fabricated by utilizing the buckling of a prestressed thin polysilicon film. The enhanced rigidity of the dome structure leads to a significant increase of its resonant frequency compared to a flat plate resonator. The shell-type geometry of the structure also provides an imbedded actuation mechanism. Significant out-of plane deflections are actuated by mechanical stress introduced within the plane of the shell. We demonstrate that thermomechanical stress generated by a focused laser beam, or microfabricated resistive heater, provides an effective and fast mechanism to operate the dome as an acoustic resonator in the radio-frequency range. All-optical operation of the shell resonator and an integrated approach are discussed.
Optical actuation of micromirrors fabricated by the micro-origami technique
Authors: Zanardi Ocampo José M. , Vaccaro Pablo O. , Fleischmann Thomas , Wang Te-Sheng , Kubota Kazuyoshi , Aida Tahito , Ohnishi Toshiaki , Sugimura Akira , Izumoto Ryo , Hosoda Makoto , Nashima Shigeki
Published: October 2003

Micromirrors were fabricated by the micro-origami technique. This technique allows the fabrication of simple and robust hinges for movable parts, and it can be applied to any pair of lattice mismatched epitaxial layers, in semiconductors or metals. A multilayer structure, including AlGaAs/GaAs component layers and an InGaAs strained layer, was grown by molecular beam epitaxy on a GaAs substrate. After definition of the hinge and mirror’s shape by photolithography, the micromirrors were released from the substrate by selective etching. They moved to their final position powered by the strain release in the InGaAs layer. Optical actuation was achieved by irradiation with the 488 nm line of an argon laser, and the mirror’s position was measured by sensing the reflection of a He–Ne laser. Continuous wave irradiation with a power density of 450 mW/mm2 produced an angular deflection of the mirror of around 0.5°. The frequency response of the mirrors shows a resonance at 25 kHz.
Experimental study of radiation induced electromotive force effects on mineral insulated cables
Authors: Van Nieuwenhove R. , Vermeeren L.
Published: October 2003

Measurements of radiation induced electromotive force (RIEMF) effects on mineral insulated cables in a pure gamma field and in a combined neutron and gamma field are presented and compared to model calculations. The effect of materials in the immediate surroundings of the cable, as predicted by the model calculations, is clearly demonstrated. In a fission reactor environment, delayed current contributions due to the neutron activation and subsequent beta emission in base materials as well as in impurities such as Mn are clearly observed and are well reproduced by model calculations. The prediction of the gamma induced current component was severely complicated by its strong sensitivity to the detailed geometry and the spectrum and the directivity of the gamma field. Although the RIEMF effect on MI cables can therefore in general not be completely eliminated, some guidelines are provided to minimize them.
Photodissociation of the OD radical at 226 and 243 nm
Authors: Radenović Dragana Č. , van Roij André J. A. , Chestakov Dmitri A. , Eppink André T. J. B. , ter Meulen J. J. , Parker David H. , van der Loo Mark P. J. , Groenenboom Gerrit C. , Greenslade Margaret E. , Lester Marsha I.
Published: October 2003

The photodissociation dynamics of state selected OD radicals has been examined at 243 and 226 nm using velocity map imaging to probe the angle–speed distributions of the D(2S) and O(3P2) products. Both experiment and complementary first principle calculations demonstrate that photodissociation occurs by promotion of OD from high vibrational levels of the ground X 2Π state to the repulsive 1 2Σ− state.
Inherent nature of localized states in highly planar monolayer InAs/GaAsN pseudo-alloys
Authors: Krestnikov I. L. , Heitz R. , Ledentsov N. N. , Hoffmann A. , Mintairov A. M. , Kosel T. H. , Merz J. L. , Soshnikov I. P. , Ustinov V. M.
Published: October 2003

We have studied the optical properties of pseudo-alloy monolayer InAs/GaAsN superlattices with highly planar interfaces. In spite of the two-dimensional growth mode, we found that the photoluminescence (PL) reveals strong exciton localization through the whole PL band, dominating the spectrum up to high excitation densities and observation temperatures. Pump-and-probe PL experiments provide the following time constants: (a) the exciton relaxation time to the ground states of the localization regions is found to be ∼40–70 ps, depending on the photon energy, and (b) the time for depopulation of these localized states is between 2 and 4 ns.
Continuum radiation from electron-dust-chain collisions in dusty plasmas
Authors: Jung Young-Dae
Published: October 2003

The bremsstrahlung emission due to collisions of nonrelativistic electrons with chains of strongly coupled dust grains in a plasma is investigated in dusty plasmas. The dust chain is considered as the one-dimensional model for strongly coupled dusty plasmas. The Born approximation is assumed for the initial and final states of the projectile electron and coherent effects are considered. The result shows that the radiation cross section is greater for smaller dust spacing for soft photon regions. This work shows a possibility of the low energy continuum radiation due to the electron-dust-chain collisions in dusty plasmas.
Spectroscopic characterization of HOONO and its binding energy via infrared action spectroscopy
Authors: Pollack Ilana B. , Konen Ian M. , Li Eunice X. J. , Lester Marsha I.
Published: October 2003

The trans–perp conformer of peroxynitrous acid is identified by action spectroscopy in the OH overtone region and assigned by simulating its band structure using a transition moment and rotational constants from ab initio theory. The highest observed OH product state sets an upper limit for the O–O bond energy of tp-HOONO of 16.8 kcal/mol.
Chemical imaging of interfaces by sum-frequency generation microscopy: Application to patterned self-assembled monolayers
Authors: Kuhnke K. , Hoffmann D. M. P. , Wu X. C. , Bittner A. M. , Kern K.
Published: October 2003

We demonstrate molecule-specific imaging of a chemically patterned self-assembled monolayer by IR-visible sum-frequency microscopy. The pattern on an Au substrate consists of microcontact printed 10 μm wide alkanethiolate stripes embedded in ω-carboxyalkanethiolate adsorbed from solution. We use both electronic and vibrational contrast mechanisms for a quantitative analysis of thiolate density and the coverage of the two molecular species. The evaluation of images taken at three different IR wavelengths suggests a substantial intermixing of the two thiolates occuring in the preparation procedure.
InAs quantum dots on the GaAs(5¯ 2¯ 11¯)B surface
Authors: Temko Y. , Suzuki T. , Xu M. C. , Jacobi K.
Published: October 2003

We report on InAs quantum dots grown by molecular-beam epitaxy on the stable GaAs(5̄ 2̄ 11¯)B surface discovered recently. Atomically resolved scanning tunneling microscopy images acquired in situ reveal compact quantum dots terminated by (1̄01̄), (01̄1̄), and (1̄1̄1̄)B facets and an unresolved vicinal (001̄) region. A flat base of (3̄1̄5̄)B orientation extends in front of the (1̄01̄) and (1̄1̄1̄)B facets. The quantum dots exhibit a very narrow size distribution attributed to the well ordered substrate and to high nucleation efficiency.
Nonrandom percolation behavior of grain boundary networks in high-Tc superconductors
Authors: Frary M. , Schuh C. A.
Published: October 2003

The grain boundary networks of tetragonal and orthorhombic superconductors are shown to be nonrandom through computer simulations of polycrystalline structures. For biaxially textured microstructures, the distribution of low-angle grain boundaries around triple junctions is measurably deviant from the expectations for a randomly constructed lattice. Percolation thresholds are calculated for the unhindered flow of superconducting current through a polycrystal, and are found to be significantly different from the standard random percolation threshold in two dimensions. These deviations are explained as a result of crystallographic constraints on the network topology.
Behavior of magnetic domains during structural transformations in Ni2MnGa ferromagnetic shape memory alloy
Authors: Park H. S. , Murakami Y. , Shindo D. , Chernenko V. A. , Kanomata T.
Published: October 2003

Change in the magnetic domain structure of Ni2MnGa Heusler alloy with the structural transformation from the parent phase to the intermediate phase and subsequent transformation to the martensite was studied by in situ observations using Lorentz microscopy and electron holography. Both the parent phase and the intermediate phase showed peculiar stripe magnetic domains, and the observed magnetization distribution was similar to each other. In contrast, the magnetization distribution was dramatically modified by the transformation to the tetragonal martensite. The observation appears to indicate that the magnetization distribution in the parent phase can interact with the short-wave lattice distortions to generate the intermediate phase, via the magnetoelastic interaction, resulting in the inheritance of the original magnetization distribution into the intermediate phase.
Dynamics of the gas–liquid interfacial reaction of O(3P) atoms with hydrocarbons
Authors: Kelso Hailey , Köhler Sven P. K. , Henderson David A. , McKendrick Kenneth G.
Published: October 2003

We describe an experimental approach to the determination of the nascent internal state distribution of gas-phase products of a gas–liquid interfacial reaction. The system chosen for study is O(3P) atoms with the surface of liquid deuterated squalane, a partially branched long-chain saturated hydrocarbon, C30D62. The nascent OD products are detected by laser-induced fluorescence. Both OD (v′=0) and (v′=1) were observed in significant yield. The rotational distributions in both vibrational levels are essentially the same, and are characteristic of a Boltzmann distribution at a temperature close to that of the liquid surface. This contrasts with the distributions in the corresponding homogeneous gas-phase reactions. We propose a preliminary interpretation in terms of a dominant trapping-desorption mechanism, in which the OD molecules are retained at the surface sufficiently long to cause rotational equilibration but not complete vibrational relaxation. The significant yield of vibrationally excited OD also suggests that the surface is not composed entirely of –CD3 endgroups, but that secondary and/or tertiary units along the backbone are exposed.
Well-ordered arrays of pyramid-shaped ferroelectric BaTiO3 nanostructures
Authors: Ma Wenhui , Harnagea Catalin , Hesse Dietrich , Gösele Ulrich
Published: October 2003

Monolayers of monodisperse latex spheres of micron size were used as deposition masks to fabricate arrays of ferroelectric nanostructures by pulsed laser deposition using a BaTiO3 target. First, arrays of well-ordered structures were prepared on SrTiO3:Nb (100) single-crystal substrates at room temperature. Investigations of these isolated as-deposited nanostructures by atomic force microscopy revealed that they have a pyramid-like shape with about 200 nm lateral size at half their height and form a regular hexagonal pattern. Then postdeposition annealing was used to crystallize the nanostructures. The ferroelectric properties of the crystalline structures were investigated by scanning force microscopy in piezoresponse mode. Piezoelectric hysteresis loops were recorded, demonstrating that the barium titanate nanopyramids have a remanent polarization and are switchable by an electric field, i.e., they are indeed ferroelectric.
A method for evaluating workplace utility
Authors: Pinder James , Price If , Wilkinson Sara J. , Demack Sean
Published: October 2003

Acquiring office buildings that provide the required level of utility, and maintaining the buildings in that state, should be a priority for any organisation. Failure to do so may give rise to increased churn, reduced productivity, higher employee turnover, increased staff absenteeism and rising health care costs related to heightened stress. There is, however, no single measure of office building utility. Discusses the development of a valid and reliable scale for measuring the utility of public sector office buildings. Data collection involved the use of focus groups and an online survey of 1,800 building occupants. The findings suggest that the utility of public sector office buildings can be measured using a 22‐item scale comprising four dimensions. The potential applications of the scale and its use in current research are examined.
Records management: France in search of a direction
Authors: Fuzeau Pierre
Published: October 2003

This article reviews the late emergence of records management in France and its recent development through the impact of the e‐environment and international standards and through the dominance of the French public‐sector approach to, and practice of, RM. The French government has launched the French “administration” on the road to e‐government, a strategy that will impact on the private sector in its relations with regulatory and other state bodies.
A Four-Base Paired Genetic Helix with Expanded Size
Authors: Liu Haibo , Gao Jianmin , Lynch Stephen R. , Saito Y. David , Maynard Lystranne , Kool Eric T.
Published: October 2003

We describe a new molecular class of genetic-pairing system that has a native DNA backbone but has all four base pairs replaced by new, larger pairs. The base pairs include size-expanded analogs of thymine and of adenine, both extended by the width of a benzene ring (2.4 Å). The expanded-diameter double helices are more thermodynamically stable than the Watson-Crick helix, likely because of enhanced base stacking. Structural data confirm a right-handed, double-stranded, and base-paired helical form. Because of the larger base size, all the pairs of this helical system are fluorescent, which suggests practical applications in detection of natural DNA and RNA. Our findings establish that there is no apparent structural or thermodynamic prohibition against genetic systems having sizes different from the natural one.
Immunotherapeutic Approaches to Alzheimer's Disease
Authors: Monsonego Alon , Weiner Howard L.
Published: October 2003

Although neurodegenerative diseases such as Alzheimer's disease are not classically considered mediated by inflammation or the immune system, in some instances the immune system may play an important role in the degenerative process. Furthermore, it has become clear that the immune system itself may have beneficial effects in nervous system diseases considered neurodegenerative. Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for the treatment of Alzheimer's disease. These studies have led to human trials that resulted in both beneficial and adverse effects. In animal models, it has also been shown that immunotherapy designed to induce a cellular immune response may be of benefit in central nervous system injury, although T cells may have either a beneficial or detrimental effect depending on the type of T cell response induced. These areas provide a new avenue for exploring immune system–based therapy of neurodegenerative diseases and will be discussed here with a primary focus on Alzheimer's disease. We will also discuss how these approaches affect microglia activation, which plays a key role in therapy of such diseases.
Is the Fragility of a Liquid Embedded in the Properties of Its Glass?
Authors: Scopigno Tullio , Ruocco Giancarlo , Sette Francesco , Monaco Giulio
Published: October 2003

When a liquid is cooled below its melting temperature, it usually crystallizes. However, if the quenching rate is fast enough, the system may remain in a disordered state, progressively losing its fluidity upon further cooling. When the time needed for the rearrangement of the local atomic structure reaches approximately 100 seconds, the system becomes “solid” for any practical purpose, and this defines the glass transition temperature
T
g
. Approaching this transition from the liquid side, different systems show qualitatively different temperature dependencies of the viscosity, and accordingly they have been classified by introducing the concept of “fragility.” We report experimental observations that relate the microscopic properties of the glassy phase to the fragility. We find that the vibrational properties of the glass well below
T
g
are correlated with the fragility value. Consequently, we extend the fragility concept to the glassy state and indicate how to determine the fragility uniquely from glass properties well below
T
g
.
Larsen Ice Shelf Has Progressively Thinned
Authors: Shepherd Andrew , Wingham Duncan , Payne Tony , Skvarca Pedro
Published: October 2003

The retreat and collapse of Antarctic Peninsula ice shelves in tandem with a regional atmospheric warming has fueled speculation as to how these events may be related. Satellite radar altimeter measurements show that between 1992 and 2001 the Larsen Ice Shelf lowered by up to 0.27 ± 0.11 meters per year. The lowering is explained by increased summer melt-water and the loss of basal ice through melting. Enhanced ocean-driven melting may provide a simple link between regional climate warming and the successive disintegration of sections of the Larsen Ice Shelf.
Direct Atom-Resolved Imaging of Oxides and Their Grain Boundaries
Authors: Zhang Zaoli , Sigle Wilfried , Phillipp Fritz , Rühle Manfred
Published: October 2003

Using high-resolution transmission electron microscopy, we obtained structure images of strontium titanate (SrTiO
3
) with a clearly resolved oxygen sublattice along different crystallographic directions in the bulklattice and for a Σ3 tilt grain boundary. Comparison with image simulations showed that the grain boundary contains oxygen vacancies. Measurements of atom displacements near the grain boundary revealed close correspondence with theoretical calculations.
Homann magnetic flow and heat transfer with uniform suction or injection
Authors: Attia H A
Published: October 2003

The steady axisymmetric flow of an incompressible viscous electrically conducting fluid impinging on a permeable flat plate with heat transfer is investigated. An external uniform magnetic field as well as a uniform suction or injection are applied normal to the plate, which is maintained at a constant temperature. Numerical solutions for the governing momentum and energy equations are obtained. The effect of the magnetic field and the uniform suction or injection on both the flow and heat transfer is presented and discussed.PACS Nos.: 47.50, 47.15
Scattering from a slit in a biisotropic medium
Authors: Hayat T , Asghar S , Hutter K
Published: October 2003

An analytical solution is developed for spherical wave scattering by a slit in an infinitely perfectly conducting sheet in a homogeneous biisotropic medium. Interestingly, the vector diffraction problem is reduced to the scattering of a single scalar field, this scalar field being the normal component of either a left-handed or a right-handed Beltrami field. The point source is assumed to be far from the slit so that the incident spherical wave is locally plane. The slit is wide and the sheet thin, both with respect to wavelength. By using the Fourier transform technique the boundary-value problem is transformed into WienerHopf equation that is solved approximately. The diffracted wave field is studied in the far field of the slit. The diffracted field is the sum of the wave fields produced by the two edges of the slit and an interaction wave field.PACS Nos.: 41.20.q, 41.20.Jb, 52.35.Hr
Contributions of high-n dielectronic satellites to krypton K-shell emission spectra
Authors: El-Machtoub G
Published: October 2003

We report here on the calculation of dielectronic recombination resonance strengths for high-lying K-shell resonance states of He-, Li-, and Be-like krypton ions. For proper analysis of spectral data explicit calculations of satellite intensity factors are carried out for all possible intermediate resonance states with n = 210. Our calculations successfully predict the details of X-ray emission spectra of highly charged krypton ions interacting with electron beams.PACS Nos.: 32.30.Rj, 32.70.Cs, 32.80.Rm, 34.79.+e
Gene Therapy for Inborn and Acquired Immune Deficiency Disorders
Authors: Engel Barbara C. , Kohn Donald B.
Published: October 2003

Gene therapy has been under development as a way to correct inborn errors for over 20 years. Immune deficiencies are favorable candidates for gene therapy because of the potential selective advantage of genetically corrected cells in these conditions. Gene therapy for immune deficiencies has been the only application to show incontrovertible benefit in clinical trials to date. Despite the success in treating the underlying disease, there have been two cases of insertional oncogenesis reported in one of these early phase trials. Gene therapy approaches and clinical trials for several inborn as well as acquired immune deficiencies will be reviewed.
Gene Therapy Targeting Hematopoietic Cells: Better Not Leave It to Chance
Authors: Baum Christopher , von Kalle Christof
Published: October 2003

Gene therapy targeting hematopoietic cells has arrived at a new stage of potency. While the potential for curing inherited disorders of the immune system has been demonstrated in clinical trials, we were also confronted with the first serious adverse events related to random insertion of foreign DNA into cellular chromosomes. As it is likely that the manifestation of severe side effects results from a multifactorial process, it will be of crucial importance to define the significance of the individual risk factors involved. The future of the field will depend on our ability to define risk classifications of clinical approaches, to continuously improve transgene technologies, and to introduce new concepts for targeted selection of transgenic cells. Interestingly, correction of genetic disorders by homologous gene repair in defined stem cell clones is on the horizon, but far from being available for clinical use.
Alternative Concepts of Suicide Gene Therapy for Graft-versus-Host Disease after Adoptive Immunotherapy
Authors: Kramm Christof M.
Published: October 2003

T-cell suicide gene therapy represents a promising novel treatment strategy for graft-versus-host disease following adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation. The clinical efficiency of this approach is still hampered by several obstacles including induction of alloresponses due to the use of immunogenic suicide and selection genes, genetic inactivation of suicide genes, and functional immunological impairment after retroviral transduction with extensive in vitro stimulation. New concepts as possible solutions to these limitations are discussed.
Adoptive T-Cell Therapy for EBV-Associated Post-Transplant Lymphoproliferative Disease
Authors: Bollard Catherine M. , Savoldo Barbara , Rooney Cliona M. , Heslop Helen E.
Published: October 2003

Increased understanding of the mechanisms by which T lymphocytes recognize virus and tumor-specific antigens has fueled the use of adoptive immunotherapy for viral and malignant diseases. An ideal candidate for such treatment is Epstein-Barr virus (EBV). EBV-associated post-transplant lymphoproliferative disorder (PTLD) is a serious complication post-solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). The disease is essentially the result of suppression of cytotoxic T-cell function and despite various treatment strategies the course may still be fulminant and lethal. Therefore, an adoptive immunotherapeutic approach using ex vivo derived EBV-specific CTL offers a promising solution not only for the treatment but also as prophylaxis for PTLD. The infusion of EBV-CTL has been demonstrated to be safe and effective in allogeneic HSCT recipients and their use post-SOT is being evaluated.
Adoptive T-Cell Therapy for Epstein-Barr Virus-Positive Hodgkin’s Disease
Authors: Huls M. Helen , Rooney Cliona M. , Heslop Helen E.
Published: October 2003

Immunotherapy approaches with antigen-specific cytotoxic T lymphocytes (CTLs) have proved safe and effective prophylaxis and treatment of Epstein-Barr virus (EBV)-associated lymphomas arising after bone marrow transplantation. EBV is also associated with other malignancies including about 40% of cases of Hodgkin’s disease making this tumor another potential target for EBV-targeted immunotherapy. While studies with autologous EBV-specific CTLs have shown antiviral activity and immune effects, the clinical responses have been less impressive than those observed in post-transplant lymphomas. There are several possible reasons why the malignant cells in EBV-positive Hodgkin’s disease may be less susceptible to immunotherapy approaches, including the fact that they express a more restricted array of EBV-encoded antigens and possess many immune evasion strategies. A number of approaches to overcome these tumor evasion strategies including targeting CTLs to the expressed antigens and genetic modification of CTLs are being evaluated.
Chimeric T-Cell Receptors for the Targeting of Cancer Cells
Authors: Rössig Claudia , Brenner Malcolm K.
Published: October 2003

Genetic engineering of human T lymphocytes to express tumor antigen-specific chimeric immune receptors is an attractive means for providing large numbers of effector cells for adoptive immunotherapy. Major mechanisms of tumor escape from immune recognition are efficiently bypassed. Although adoptive transfer of chimeric receptor-expressing peripheral blood-derived T lymphocytes has produced some anti-tumor activity in mice, the first clinical studies have revealed a disappointing lack of correlation between in vitro cytotoxicity and therapeutic efficacy. The most pertinent issue is that chimeric T cells fail to expand and rapidly lose their function in vivo. Potential strategies to enhance the therapeutic value of chimeric receptor-modified cells by preventing their functional inactivation in vivo are currently being investigated.
Side Effects of Ifosfamide
Authors: Klastersky J.
Published: October 2003

Ifosfamide is relatively well tolerated but it can be associated occasionally with life-threatening complications such as arrhythmias and heart failure, severe encephalopathy and hemorrhagic cystitis. Mesna administration can control the urothelial toxicity of ifosfamide, but it is without effect on the other complications. Other preventive measures, such as amifostine or methylene blue administration, have not yet been adequately evaluated in a sufficient number of patients. Clinicians prescribing ifosfamide, especially in high doses, should be watchful for early signs of toxicity in order to discontinue ifosfamide administration soon enough to avoid development of major toxicity.
Ifosfamide and Cyclophosphamide: Effects on Immunosurveillance
Authors: Binotto G. , Trentin L. , Semenzato G.
Published: October 2003

Ifosfamide (IF) and cyclophosphamide (CTX) are chemotherapeutic agents frequently used in the treatment of human malignancies. These drugs can exhibit a bimodal mechanism of antitumor action with cytotoxic and immunomodulatory effects when associated with adoptive immunotherapy. In human peripheral blood lymphocytes, IF irreversibly inhibits the proliferative response to interleukin-2 in a dose-dependent manner and may also induce the phosphorylation of HSP27 by depleting glutathione. CTX promotes discrete cytokine profiles upregulating the expansion of Th1 cells, and this may be important to increase cellular immune response. The data presented in this report indicate that treatment regimens of CTX and IF may be used according to the tumor immunogenicity.
Ifosfamide in Small Cell Lung Cancer
Authors: Marangolo M. , Giovanis P.
Published: October 2003

Recent literature about the treatment options of small cell lung cancer stresses the role of ifosfamide both alone and in combination with either cisplatin or carboplatin and etoposide. Its pharmacokinetics and the lower hematological toxicity permit the use of high doses which seem to be more effective in this very sensitive tumor. However, despite the increment in the response rate, in both limited and extended disease, the overall and long-term survival seems to be little influenced by therapy. Newer strategies combining old and new therapeutic approaches have to be explored to overcome the lack of progresses registered in these years.
Role of Ifosfamide in Cervical Cancer: An Overview
Authors: Buda A. , Dell’Anna T. , Signorelli M. , Mangioni C.
Published: October 2003

Ifosfamide, a cyclophosphamide analogue, has demonstrated a wide spectrum of activity against numerous neoplasms in different oncologic areas, including paediatric, haematological, breast, lung and testicular cancers, soft tissue sarcomas and gynaecological cancer. In gynaecologic cancers in particular, evidence suggests activity in the treatment of epithelial ovarian cancer, cervical carcinoma, germ cell carcinoma of the ovary. Cervical cancer has long been considered a poorly chemosensitive tumour and for several years the role of chemotherapy in the treatment of this tumour was confined to persistent or recurrent disease after failure of surgery and/or radiotherapy. In the management of cervical cancer, chemotherapy has received increasing attention in the last two decades and is currently used in neoadjuvant regimens, as salvage treatment in patients with disseminated or recurrent disease, or as a radiosensitizer. Over the past 30 years, several agents have been tested but cisplatin and ifosfamide are the agents that have attracted the greater attention. Cisplatin represents the cornerstone of chemotherapy for cervical cancer. Ifosfamide has been studied as a single agent or in combination with other drugs in different studies. In this paper we reviewed the approach with systemic therapy and, in particular, the role of ifosfamide in advanced or recurrent, and less advanced cervical cancer.
Ifosfamide in Pediatric Solid Tumors
Authors: Carli M. , Passone E. , Perilongo G. , Bisogno G.
Published: October 2003

Phase II studies conducted in Europe and the USA on pediatric solid tumors have shown that ifosfamide, as a single agent, is an active drug against a variety of neoplasms – rhabdomyosarcoma (RMS), some non-RMS soft tissue sarcomas, Wilms’ tumor, bone sarcomas and neuroblastoma. Furthermore, an increase in tumor response rate has been observed when ifosfamide has been used in combination with other drugs. The usual dose of ifosfamide varies from 1.8 to 3 g/m2/day for 2–5 days according to the different regimens. Some controversies still exist on the modality of drug administration and more precisely on the time of infusion, however in pediatric practice, short infusion (e.g. 3 h) is usually preferred because of the reduced neurotoxicity in comparison to lengthier administration (e.g. 24 h). Ifosfamide is currently included in the standard therapy of pediatric bone and soft tissue sarcomas. It is also used in a selected high-risk group of patients with Wilms’ tumor, neuroblastoma and germ cell tumors.
Minilaparotomy May Be Independently Associated with Reduction in Inflammatory Responses after Resection for Colorectal Cancer
Authors: Nakagoe T. , Tsuji T. , Sawai T. , Sugawara K. , Inokuchi N. , Kamihira S. , Arisawa K.
Published: October 2003

Objectives: A minilaparotomy approach (skin incision less than 7 cm) to resection of colon cancer is technically feasible, but objective data supporting its benefit are scarce. The aim of this study was to clarify whether minilaparotomy is independently associated with a reduction in the acute inflammatory response after resection of colorectal cancer. Design: Thirty-one patients who underwent surgical resection of colorectal cancer using minilaparotomy or conventional laparotomy were included in this nonrandomized prospective study. Inflammatory responses were evaluated with serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels. Results: In both the minilaparotomy and conventional laparotomy groups, serum IL-6 and CRP levels significantly increased 24 h after the operation (1POD) compared to preoperative levels (p < 0.0001 and p < 0.0001, respectively). Median serum levels of IL-6 and CRP in the minilaparotomy group were significantly lower at 1POD versus the conventional group (p = 0.0066 and p = 0.0033, respectively). Multivariate analyses showed that a smaller increase in serum IL-6 or CRP levels at 1POD [less than 75th percentile (112.9 or 10.6 mg/ml, respectively)] was independently related to only minilaparotomy. Conclusions: These data in this nonrandomized trial suggest that minilaparotomy may be independently associated with reduced inflammatory responses in colorectal cancer resection.
Chased PCR: A Modified Inverse PCR Technique to Characterize Flanking Regions of AT-Rich DNA Fragments
Authors: Shams-Eldin Hosam , Debierre-Grockiego Françoise , Schwarz Ralph T.
Published: October 2003

The chased polymerase chain reaction (PCR) technique described here is a convenient method enabling the characterization of flanking regions of a known A/T-rich DNA fragment in two different successive steps. The first step includes a modified inverse PCR with inverted tail-to-tail primers, each with 35 overhanging nucleotides for the insertion into a carrier plasmid. The second step consists of a technique similar to a site-directed mutagenesis. The chased PCR technique is simple, quick, versatile and efficient; it improves the inverse PCR technique and may be applied to any ligation-linker method. Consequently, the techniques for PCR-based gene isolation are more suitable for the isolation of missing sequences of A/T-rich or complex DNA.
Analysis of the Elements of Catabolite Repression in Clostridium acetobutylicum ATCC 824
Authors: Tangney Martin , Galinier Anne , Deutscher Josef , Mitchell Wilfrid J.
Published: October 2003

The ptsH gene, encoding the phosphotransferase protein HPr, from Clostridium acetobutylicum ATCC 824 was identified from the genome sequence, cloned and shown to complement a ptsH mutant of Escherichia coli. The deduced protein sequence shares significant homology with HPr proteins from other low-GC gram-positive bacteria, although the highly conserved sequence surrounding the Ser-46 phosphorylation site is not well preserved in the clostridial protein. Nevertheless, the HPr was phosphorylated in an ATP-dependent manner in cell-free extracts of C. acetobutylicum. Furthermore, purified His-tagged HPr from Bacillus subtilis was also a substrate for the clostridial HPr kinase/phosphorylase. This phosphorylation reaction is a key step in the mechanism of carbon catabolite repression proposed to operate in B. subtilis and other low-GC gram-positive bacteria. Putative genes encoding the HPr kinase/phosphorylase and the other element of this model, namely the catabolite control protein CcpA, were identified from the C. acetobutylicum genome sequence, suggesting that a similar mechanism of carbon catabolite repression may operate in this industrially important organism.
MRAD: Metabolic Reaction Analysis Database – An Entity-Relationship Approach
Authors: Lall Raman , Gao Guang , Dhurjati Prasad , Edwards Jeremy
Published: October 2003

The Metabolic Reaction Analysis Database (MRAD) is a relational database based on the Entity-Relationship (ER) model which combines information about organisms, biochemical pathways, reactions, enzymes, substrates, products and genes. It describes 244,596 genes in 79 organisms, 6,552 enzymes, and 3,552 reactions, 3,100 substrates, 2,866 products and 118 metabolic pathways. The MRAD graphical user interface allows for the identification of metabolic reactions which are similar and dissimilar in multiple organisms, reactions in a pathway which are missing in an organism and using any combination between one to six of the biological entities of organisms, genes, pathways, enzymes, substrates and products to determine metabolic reactions. MRAD provides a powerful and efficient tool for the construction of flux balance models for metabolic engineering applications.
Novel Transporters from Hemiascomycete Yeasts
Authors: De Hertogh Benoît , Talla Emmanuel , Tekaia Fredj , Beyne Emmanuelle , Sherman David , Baret Philippe V. , Dujon Bernard , Goffeau André
Published: October 2003

We screened nearly one thousand random sequenced targets obtained by partial sequencing of 13 hemiascomycete genomes identified by higher amino acid sequence similarity to a non-Saccharomyces cerevisiae protein than to a S. cerevisiae protein. Among those sequences we have identified 36 novel phylogenetic clusters of putative transporters which, according to the Transport Commission system (TC-DB, 2002; http:// tcdb.ucsd.edu/tcdb), do not belong to acknowledged S. cerevisiae protein families [De Hertogh et al.: Funct. Integr. Genomics 2002;2:154–170; http://cbi.labri.u-bordeaux.fr/Genolevures]. These novel hemiascomycete transporters comprise 3 channels, 23 secondary transporters, 5 primary transporters and 5 membrane proteins of unknown function.
New Antibiotic Resistance Cassettes Suitable for Genetic Studies in Borrelia burgdorferi
Authors: Elias Abdallah F. , Bono James L. , Kupko III John J. , Stewart Philip E. , Krum Jonathan G. , Rosa Patricia A.
Published: October 2003

In this report we describe two distinct approaches to develop new antibiotic resistance cassettes that allow for efficient selection of Borrelia burgdorferi transformants. The first approach utilizes fusions of borrelial flagellar promoters to antibiotic resistance markers from other bacteria. The aacC1 gene, which encodes a gentamicin acetyltransferase, conferred a high level of gentamicin resistance in B. burgdorferi when expressed from these promoters. No cross-resistance occurred between this cassette and the kanamycin resistance cassette, which was previously developed in an analogous fashion. A second and different approach was taken to develop an efficient selectable marker that confers resistance to the antibiotic coumermycin A1. A synthetic gene was designed from the gyrB301 allele of the coumermycin-resistant B. burgdorferi strain B31-NGR by altering the coding sequence at the wobble position. The resulting gene, gyrBsyn, encodes a protein identical to the product of gyrB301, but the genes share only 66% nucleotide identity. The nucleotide sequence of gyrBsynis sufficiently divergent from the endogenous B. burgdorferigyrB gene to prevent recombination between them. The cassettes described in this paper improve our repertoire of genetic tools in B. burgdorferi. These studies also provide insight into parameters governing recombination and gene expression in B. burgdorferi.
Mutations in the N-Terminus of the Major Coat Protein (pVIII, gp8) of Filamentous Bacteriophage Affect Infectivity
Authors: Li Zhenpeng , Koch Holger , Dübel Stefan
Published: October 2003

Filamentous bacteriophages are nonlytic, male-specific bacteriophages which infect Escherichia coli carrying an F-episome. The molecular mechanism of infection remains elusive, including the role of the major coat protein pVIII. In order to evaluate the contributions of major coat protein pVIII in the process of infection, two phage display libraries were generated. One library consisted of random amino acids at positions 2, 4, 5, 8, 11 and 12 of the N-terminus of major coat protein pVIII. The second library was generated by randomizing these positions as well as position 1. All these residues were previously shown to be exposed at the surface of the virions by being accessible to ligands. The infectivity of randomly selected mutant phages was analyzed. The present results demonstrate that phages modified at these positions can be correctly assembled and secreted into the exoplasm, although the efficiency was slightly lower than that of wild-type phage. Their infectivity varied greatly, and a general structural pattern underlying infectivity did not emerge. However, residual differences were observed between infectious and defective phage; in general, uncharged polar amino acids present at positions 5 and 11 of the N-terminus of pVIII reduced phage infectivity, whereas polar residues at position 8 facilitated infection. The first position of pVIII is remarkably critical for infection; when this alanine was substituted with other residues, most of the phages lost their infectivity. These results shed new light on the true complexity of random peptide pVIII phage display libraries.
Relationship between Natriuretic Peptides and Residual Diuresis during Continuous Hemodiafiltration
Authors: Balík Martin , Jabor Antonín , Kolář Michal , Pavlisová Marie , Břešt’an Daniel , Hendl Jan , Rychlík Ivan , Pachl Jan
Published: October 2003

Background: The reasons for the decrease or increase of urine output following the start of continuous venovenous hemodiafiltration (CVVHDF) have not yet been explained sufficiently. The renoprotective properties of natriuretic peptides were described. Methods: The levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in 23 mechanically ventilated patients before and during the first 48 h of CVVHDF. Samples were drawn both from the ports proximal and distal to the filter. The results were compared between the group where daily diuresis (Vu) remained low or decreased and the group where diuresis increased to the level of 1.5 ml·kg–1·h–1 or higher after 48 h of treatment. Left ventricular dysfunction (LVD) was defined as LV ejection fraction below 40%. A control group consisted of 10 patients exposed to abdominal surgery. Results: The average AVdiff (%) of ANP and BNP on filter were insignificant. Patients with increasing diuresis (n = 12) had significantly lower levels of both ANP (p < 0.001) and BNP (p < 0.005) than the patients with decreasing diuresis (n = 11). Significant correlations were revealed for ANP and Vu (p < 0.01) and for BNP and Vu (p < 0.05). The levels of both peptides were grossly elevated in comparison to controls and were predictive of survival. The differences between cardiac and non-cardiac patients were significant both for ANP and for BNP. Conclusions: The elimination of ANP and BNP by the CVVHDF is negligible. The levels of natriuretic peptides are inversely related to Vu and predict survival. ANP and BNP levels correlate with left ventricular function even during acute renal failure and CVVHDF.