bluuebunny/crossref_metadata_2025 huggingface dataset:
A smooth permittivity function for Poisson–Boltzmann solvation methods
Authors: Grant J. Andrew , Pickup Barry T. , Nicholls Anthony
Published: October 2004

This work introduces a continuous smooth permittivity function into Poisson–Boltzmann techniques for continuum approaches to modeling the solvation of small molecules and proteins. The permittivity function is derived using a Gaussian method to describe volume exclusion. The new method allows a rigorous determination of solvent forces within a grid‐based technology. The generality of approach is demonstrated by considering a range of applications for small molecules and macromolecules. We also present a very complete statistical analysis of grid errors, and show that the accuracy of our Gaussian‐based method is improved over standard techniques. The method has been implemented in a new code called ZAP, which is freely available to academic institutions.1 © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 608–640, 2001
Ab initioquantum chemistry and molecular dynamics simulations studies of LiPF6/poly(ethylene oxide) interactions
Authors: Borodin Oleg , Smith Grant D. , Jaffe Richard L.
Published: October 2004

Ab initioand molecular mechanics studies of LiPF6and the interaction of the salt with the poly(ethylene oxide) (PEO) oligomer dimethylether have been performed. Optimized geometries and energies of Li+/PF6−complexes obtained from quantum chemistry revealed a preference for C3Vsymmetry structures for Li+–P separations under 2.8 Å, C2Vsymmetry for Li+–P in the range of 2.8–3.3 Å and C4Vsymmetry for Li+–P separations larger than 3.3 Å. Electron correlation effects were found to make an insignificant contribution to binding in the Li+/PF6−complex. By contrast, analogous studies of PF6−/PF6−and PF6−/dimethyl ether complexes revealed important contributions of electron correlation to the complex interaction energy. A molecular mechanics force field for simulations of PEO/LiPF6melts was parameterized to reproduce the geometries and energies of Li+/PF6−, PF6−/PF6−, PF6−/dimethylether complexes. Molecular dynamics simulations of PEO/LiPF6melts were performed to validate this quantum chemistry‐based force field. Accurate reproduction of the increase in solution density with addition of salt was found while the electrical conductivity of PEO/LiPF6solutions was found to be within an order of magnitude of the experimental values. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 641–654, 2001
Multiscale fast summation of long‐range charge and dipolar interactions
Authors: Sandak Bilha
Published: October 2004

Here we present a linear order multiscale method for the fast summation of long range forces in a system consisting of a large number of charge and dipolar particles. For a N‐body system, our algorithm requires an order of work that is proportional to O(N), in comparison to order O(N2) of the direct pairwise computation. Our method is demonstrated on two‐dimensional homogeneous point‐charge and dipolar systems, and a combined heterogeneous particle system, for the calculation of the induced electrostatic potential and energy. The electrostatic interaction is decomposed into a local part and a smooth part. The method thus, has several potential advantages over other O(N log N) or O(N) techniques, especially for calculation with moving particles or implicit charges locations. This approach is beneficial to large‐scale problems such as molecular statics, molecular dynamics, equilibrium statistics (Monte‐Carlo simulations), molecular docking, and in areas such as magnetism and astrophysics. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 717–731, 2001
MSINDO parameterization for third‐row transition metals
Authors: Bredow Thomas , Geudtner Gerald , Jug Karl
Published: October 2004

The recently developed MSINDO version of the semiempirical SCF MO method SINDO1 has been parameterized for third‐row transition metals Sc to Zn. The set of reference data used for the previous parameterization of SINDO1 has been substantially increased by incorporating results of recent experiments and first‐principles calculations. A comparison of calculated heats of formation, geometries, ionization potentials, and dipole moments with literature values for more than 200 gas phase molecules is presented. The accuracy of the modified MSINDO version achieved for heats of formation and bond lengths has been considerably improved compared to SINDO1. Small clusters of transition metals and metal oxides were included in the parameterization to ensure accurate results for studies of larger systems. The application of the method to small transition metal complexes that were not included in the parameterization shows that the optimized parameters are transferable to other compounds. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 861–887, 2001
Application of structure‐based focusing to the estrogen receptor
Authors: Kirchhoff Paul D. , Brown Rob , Kahn Scott , Waldman Marvin , Venkatachalam C. M.
Published: October 2004

We present the Cerius2 Structure‐Based Focusing (SBF) application. This application was applied to the estrogen receptor. A series of three‐dimensional queries were generated for the binding site of the receptor. The queries consist of combinations of hydrogen bond donors and acceptors, and lipophilic features for the binding site along with excluded volume regions occupied by the receptor atoms. A database of 31 ligands with known relative binding affinities for the estrogen receptor was used to examine the selectivity of the queries. The objective of the study was to determine if queries generated by the Cerius2 SBF method could differentiate between the more and less active ligands of the training set. Results are promising, with the generated queries showing greater selectivity toward the more active ligands. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 993–1003, 2001
Adsorption integral equation via complex approximation with constraints: kernel of general form
Authors: Bushenkov Vladimir A. , Ramalho J. P. Prates , Smirnov Georgi V.
Published: October 2004

For the monolayer adsorption on a homogeneous surface, including arbitrary range lateral interactions, the isotherm can be written as a power series of the Langmuir isotherm. If this isotherm is used as the kernel in the adsorption integral equation, this integral equation can be solved in an analytical form. Because the global isotherm is usually known as a set of experimental values, the use of a numerical method is inevitable. A new numerical method for solving the adsorption integral equation with a kernel of general form is developed. It is based on recent results concerning the structure of the local isotherm and on the ideas of complex approximation with constraints, and allows reduction of the problem under consideration to a linear‐quadratic programming problem. Results of numerical experiments are presented. The method can be useful for the evaluation of the adsorption energy distribution from experimental data. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1058–1066, 2001
Analysis of the transferability of atomic multipoles for amino acids in modeling macromolecular charge distribution from fragments
Authors: Kędzierski Pawel , Sokalski W. Andrzej
Published: October 2004

Cumulative Atomic Multipole Moments were calculated for all natural amino acids and symmetric cyclic hexapeptides within Self‐Consisted Field (SCF) and Density Functional Theory (DFT) approaches using a standard 6‐31G(d,p) basis set. These data were used to analyze in detail the quality and the conformational and the intermolecular transferability of molecular charge distributions expressed in the atomic multipole form. Intermolecular interaction energies were reproduced reasonably by CAMM transformed from other conformations. Good transferability of CAMM based model was also achieved between similar molecular environments, which opens a route to modeling electrostatic effects in highly symmetric (e.g., crystalline) systems. Transferability deficiencies of various charge distribution models were analyzed and attributed to different levels of multipole expansion. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1082–1097, 2001
Cationic Closo Carboranes—Promising Weakly Coordinating Ions
Authors: Jemmis Eluvathingal D. , Ramalingam M. , Jayasree Elambalassery G.
Published: October 2004

The unexplored carbon rich cationic closo carboranes, C3Bn−3Hn+1 (n=5, 6, 7, 10, 12) are investigated theoretically. The position isomers were calculated at the B3LYP/6‐31G* level, and the charge distribution in the cluster is estimated by NBO analysis. The criterion of ring‐cap orbital overlap compatibility along with the number of BC, CC, and BB bonds help in explaining the stability order in each category. The most stable isomer is the one with maximum ring‐cap orbital overlap and largest number of BC bonds. The order of relative stability among the trigonal bipyramid is 1c>1b>1a′, where the stability is proportional to the number of CH caps over the small three‐membered ring. The C3B3H6+ isomer with the one allyl C3 group (2b) is more favorable than the one with a cyclopropenyl group (2a). Among the C3B4H7+ isomers the stability order is 3e>3d>3c>3b>3a, which mostly depends on the ring‐cap orbital overlap. In the bicapped square antiprism (4) where there is large number of isomers, the order follows the rule of ring cap compatibility and the number of BC bonds. The order of 5e>5d>5c>5b>5a obtained from the calculations is in perfect agreement with the above sited rules. Equations (1)–(5) devised for estimating the stability of isomers of C3Bn−3Hn+ indicate an increase in stability with cage size. The mono‐positive charge of the isomers is distributed throughout the cage, making them suitable candidates as weakly electrophillic cations. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1542–1551, 2001
Choice of Spin–Orbit Correction Terms in Gaussian Model Chemistries
Authors: Duke Brian J.
Published: October 2004

Spin–orbit correction terms for use in Gaussian‐2 theory and other model chemistries for third‐row atoms and molecules are calculated by several methods with the objective of finding a reliable method that can be applied in a routine and economical manner in the spirit of Gaussian model chemistries. The results are evaluated for the test set of molecules and ions used in the original extension of Gaussian‐2 theory to third‐row atoms. Further results are presented for systems where Gaussian‐2 results are reported in the literature without spin–orbit correction terms and for some larger molecules. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1552–1556, 2001
On the interaction of Mo and Mo2 with NH3, C2H4, and C3H6
Authors: Lacaze‐Dufaure Corinne , Mineva Tzonka , Russo Nino
Published: October 2004

The reactivity of Mo and Mo2 with ammonia, ethene, and propene molecules has been investigated by using Density Functional Theory. Different gradient‐corrected and hybrid exchange‐correlation functionals have been employed. Coordination modes, binding energies, geometrical structures, vibrational frequencies have been computed and compared with the available experimental counterparts. The results obtained show that the molybdenum atom is able to react with C2H4 and C3H6, and binds weakly with NH3. The dimer Mo2 gives a stable complexes with ammonia, ethene, and propene. For the Mo2NH3 complex, all the employed levels of theory give binding energies in good agreement with the experimental value, while in the case of the MoC2H4 system, the use of model core potentials coupled with gradient‐corrected exchange‐correlation functionals overestimates the binding energies. For MoC3H6, Mo2C2H4, and Mo2C3H6 we predict a binding energy of 14–15, 20–24, and 18–20 kcal/mol, respectively. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1557–1564, 2001
Systematic Study of Selected Diagonalization Methods for Configuration Interaction Matrices
Authors: Leininger Matthew L. , Sherrill C. David , Allen Wesley D. , Schaefer Henry F.
Published: October 2004

Several modifications to the Davidson algorithm are systematically explored to establish their performance for an assortment of configuration interaction (CI) computations. The combination of a generalized Davidson method, a periodic two‐vector subspace collapse, and a blocked Davidson approach for multiple roots is determined to retain the convergence characteristics of the full subspace method. This approach permits the efficient computation of wave functions for large‐scale CI matrices by eliminating the need to ever store more than three expansion vectors (bi) and associated matrix‐vector products (σi), thereby dramatically reducing the I/O requirements relative to the full subspace scheme. The minimal‐storage, single‐vector method of Olsen is found to be a reasonable alternative for obtaining energies of well‐behaved systems to within μEh accuracy, although it typically requires around 50% more iterations and at times is too inefficient to yield high accuracy (ca. 10−10 Eh) for very large CI problems. Several approximations to the diagonal elements of the CI Hamiltonian matrix are found to allow simple on‐the‐fly computation of the preconditioning matrix, to maintain the spin symmetry of the determinant‐based wave function, and to preserve the convergence characteristics of the diagonalization procedure. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1574–1589, 2001
A density functional theory study of the dimers of HX (X = F, Cl, and Br)
Authors: Rankin Kathryn N. , Boyd Russell J.
Published: October 2004

The geometries, interaction energies, and vibrational properties of (HF)2, (HCl)2, and (HBr)2 have been investigated using a variety of hybrid density functional methods and the 6‐311+G(2df,p) basis set. Although most of the density functional methods predict geometries in reasonable agreement with experiment, methods containing the LYP correlation functional yield geometrical parameters in slightly better agreement. The (HF)2 interaction energy, predicted by the hybrid density functional methods, is in reasonable agreement with experiment, but the (HCl)2 and (HBr)2 interaction energies are underestimated substantially. The frequency shift for the XH donor bond correlates linearly with the elongation of the XH bond upon complexation, and is predicted reasonably well by methods containing the LYP functional. Overall, the hybrid density functional methods adequately predict the properties of the halide dimers. It is interesting to note that the BHandHLYP and B1LYP density functional methods offer a competitive alternative to the popular B3LYP method. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1590–1597, 2001
Configuration interaction and density functional study of the influence of lithium cation complexation on vertical and adiabatic excitation energies of enones
Authors: Sunoj R. B. , Lakshminarasimhan P. , Ramamurthy V. , Chandrasekhar J.
Published: October 2004

The changes in the excited state energies of representative cyclic enones (cyclopentenone and cyclohexenone) induced by lithium ion coordination have been examined using ab initio and DFT methods. Quantitative estimates of the vertical triplet state energies were obtained using configuration interaction calculations at the CIS and CIS(D) levels with the 6‐31+G(d) basis. Inclusion of perturbative doubles corrections has a marked effect on the relative energies of the n–π* and π–π* triplet states. At both CI and CIS(D) levels, lithium complexation is predicted to raise the energy of the n–π* triplet state much more than the π–π* triplet. The trends obtained at the CIS(D) level are reproduced using B3LYP/6‐31+G(d) calculations. Adiabatic excitation energies were also computed by carrying out geometry optimization of the triplet states at the B3LYP level. While the separation between the geometry optimized n–π* and π–π* triplet states is very small for the parent enones, the π–π* triplet is clearly favored in the lithium complexes. These results suggest the possibility of reversing the reactive photoexcited state in enones through cation complexation. The conclusions provide a rationale for interesting variations in product distributions observed for enones in cation exchanged zeolites. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1598–1604, 2001
Analytical TDHF second derivatives of dynamic electronic polarizability with respect to nuclear coordinates. Application to the dynamic ZPVA correction
Authors: Quinet Olivier , Champagne Benoît , Kirtman Bernard
Published: October 2004

Analytical calculation of second derivatives of the dynamic electronic polarizability with respect to vibrational normal coordinates has been implemented at the TDHF level of approximation. Important simplifications are obtained by using the 2n+1 rule and interchange relations. In application to small molecules the first‐order ZPVA correction is found to have greater frequency dispersion than the electronic polarizability, but the former remains small in comparison. For the linear polyenes, C2nH2n+2 (n=1–3), the percentage ZPVA correction decreases with chain length for all ℏω<0.10 a.u. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1920–1932, 2001
Religious groups as diffusers of HIV antibody testing and prevention messages
Authors: Lightfoot Marguerita , Rotheram‐Borus Mary Jane , Towns Belinda , Cline Timothy R. , Webber Douglas , Murphy Debra A. , Tsai Lan Feng
Published: October 2004

Using a quasi‐experimental design, this study examined how delivering a brief training to volunteers in church congregations impacted (a) church volunteers' persistence in delivering HIV antibody testing messages over time and (b) HIV antibody testing behavior of the church volunteers themselves. Church volunteers attended a briefing regarding delivery of public health messages to others and the churches were assigned to either: (a) a trained condition, where 345 volunteers received an additional 3‐hour training in diffusing HIV prevention messages, or (b) a comparison condition, where 199 volunteers received no HIV‐specific training. Three months after the intervention, church volunteers in the HIV‐trained condition reported delivering an HIV antibody testing and prevention message to more community members than volunteers in the comparison condition. Those in the HIV‐trained condition also reported significantly higher levels of comfort and self‐efficacy in delivering HIV prevention messages than volunteers in the comparison condition. However, the trained volunteers did not themselves get tested for HIV at higher rates than the untrained volunteers. Training church volunteers for community diffusion of HIV prevention messages is an efficient strategy for diffusing HIV messages. © 2001 John Wiley & Sons, Inc.
Motion detectors in the locust visual system: From biology to robot sensors
Authors: Rind F. Claire
Published: October 2004

Motion detectors in the locust optic lobe and brain fall into two categories: neurones that respond selectively to approaching vs. receding objects and neurones that respond selectively to a particular pattern of image motion over a substantial part of the eye, generated by the locust's own movements through its environment. Neurones from the two categories can be differentiated on the basis of their response to motion at a constant velocity at a fixed distance from the locust: neurones of the first category respond equally well to motion in any direction whereas neurones in the second category respond selectively to one preferred direction of motion. Several of the motion detectors of the first category, responding to approaching objects, share the same input organisation, suggesting that it is important in generating a tuning for approaching objects. Anatomical, physiological, and modelling studies have revealed how the selectivity of the response is generated. The selectivity arises as a result of a critical race between excitation, generated when image edges move out over the eye and delayed inhibition, generated by the same edge movements. For excitation to build up, the velocity and extent of edge motion over the eye must increase rapidly. The ultrastructure of the afferent inputs onto the dendrites of collision sensitive neurones reveals a possible substrate for the interaction between excitation and inhibition. This interpretation is supported by both physiological and immunocytochemical evidence. The input organisation of these neurones has been incorporated into the control structure of a small mobile robot, which successfully avoids collisions with looming objects. The ecological role of motion detectors of the second category that respond to image motion over a substantial part of the visual field, is discussed as is the input organisation that generates this selective response. The broad tuning of these neurones, particularly at low velocities (<0.02°/s), suggests they may have a role in navigation during migratory flights at altitude. By contrast, their optimum tuning to high‐image velocities suggests these motion detectors are adapted for use in a fast flying insect, which does not spend significant time hovering. Microsc. Res. Tech. 56:256–269, 2002. © 2002 Wiley‐Liss, Inc.
Novel method for the plan‐view TEM preparation of thin samples on brittle substrates by mechanical and ion beam thinning
Authors: Sáfrán G. , Grenet T.
Published: October 2004

A new preparation method has been developed in order to avoid the breaking of brittle samples for plan‐view TEM investigation during and after mechanical and ion beam thinning. The thinning procedure is carried out on a reduced size piece of the sample (about 1.6 × 0.8 mm2 or about 1–1.6 mm diameter) that is embedded into a 3‐mm‐diameter Ti disk, which fits the sample holder of the TEM. The small sample size and the supporting metal disk assure the mechanical stability and minimize the possibility of breaking during and after the preparation: The Ti disk is placed on adhesive kapton tape, a cut piece of the sample is put into the slot of the disk, pressed onto the tape and embedded with glue. The tape keeps the parts in place and in the same plane, keeps the sample surface safe from the embedding glue and can be removed easily after the glue solidifies. Subsequently, the embedded sample is thinned from the rear by well‐known mechanical and ion beam techniques until electron transparency. This simple solution lowers the risk of failed sample preparation remarkably and makes it possible to reduce the thickness of the sample to about 50 μm by mechanical thinning. As a result, dimpling becomes unnecessary and low angle ion milling gives a large transparent area for TEM. Its efficiency has been proved by successful preparation of numerous thin film samples on Si, sapphire, and glass substrates. The method is compatible with the widespread cross‐sectional thinning procedures, and can be easily adopted by TEM laboratories. Microsc. Res. Tech. 56:308–314, 2002. © 2002 Wiley‐Liss, Inc.
Recent advances in the histochemical staining of heavy metals by means of chelating agents, with special reference to cadmium
Authors: Sumi Y. , Suzuki T.
Published: October 2004

This review discusses the way of improving the sensitivity and specificity of chelating agents used for the histochemical demonstration of trace amounts of heavy metals in cells and tissues. In the search for a more sensitive and specific agent, various chelating agents have been prepared and their staining properties for various metals examined. Of those developed 1‐(2‐benzothiazolylazo)‐2‐naphthol (BTAN), 2‐(8‐quinolylazo)‐4,5‐(diphenyl)imidazole (QAI), and 2‐(5‐bromo‐2‐pridylazo)‐5‐(diethylamino)phenol (BrPADAP) were far superior to conventional staining agents in staining sensitivity. This was particularly so for staining cadmium. When modifying chelating agents to increase staining sensitivity, hydrophobicity of the agent molecules, selection of substituent groups, and the position of the groups added to the agent molecules must be taken into consideration. The most frequently mentioned factors in a staining mechanism are complex‐tissue attractive forces, and recent studies have made it clear that weak interactions, such as hydrogen bonds and hydrophobic interactions, contribute significantly. The Hansch π values were a useful indication of the hydrophobicity of metal staining agents. The published values for stability constants of metal complexes were found to be unreliable guides for choosing a masking agent to block interfering metals. The polyphosphates, aminopolycarboxylic acids, and alkylamines were among the most useful masking agents for metal staining from a practical standpoint. Microsc. Res. Tech. 56:332–340, 2002. © 2002 Wiley‐Liss, Inc.
Photosensory transduction in unicellular eukaryote Blepharisma
Authors: Matsuoka Tatsuomi , Kotsuki Hiyoshizo
Published: October 2004

In the ciliated protozoan Blepharisma, step‐up photophobic response is mediated by a novel type of photosensory complex of pink‐colored pigment “blepharismins” and 200‐kDa membrane protein contained in the pigment granules located just beneath the plasma membrane. We found that the fluorescence intensity of isolated blepharismins decreased prominently with a decrease of H+ concentration in the surrounding medium. In the present study, therefore, we utilized the endogenous pigment blepharismins as the pH indicator. Light stimulation evoked a sudden decrease in fluorescence intensity in a photosensitive anterior portion of the cell, suggesting that a drop in H+ concentration occurred in the anterior region. The result indicates that the photosignal is transduced into cytoplasmic signaling of H+ translocation across the outer membrane surrounding the pigment granules, so that cytosolic H+ concentration in the vicinity of plasma membrane might be increased. J. Exp. Zool. 289:467–471, 2001. © 2001 Wiley‐Liss, Inc.
Thinking through war: The social thought of Richard T. Ely, John R. Commons, and Edward A. Ross during the First World War
Authors: Herzberg David
Published: October 2004

This paper examines the social thought of University of Wisconsin professors Richard T. Ely, John R. Commons, and Edward A. Ross during World War I. Like many of their fellow scholars, these three were actively involved in the pro‐war effort. Although their support for the war was strongly conditioned by personal and occupational considerations, the impact of their wartime service was not restricted to those realms. Their social thought, which they impressed into service explaining and justifying the war, was itself altered in subtle and sometimes surprising ways by the forceful positions they took on the political, economic, and racial significance of the conflict. © 2001 John Wiley & Sons, Inc.
Voxel‐based analysis of MTR images: A method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis
Authors: Audoin Bertrand , Ranjeva Jean‐Philippe , Duong My Van Au , Ibarrola Danielle , Malikova Irina , Confort‐Gouny Sylviane , Soulier Elisabeth , Viout Patrick , Ali‐Chérif André , Pelletier Jean , Cozzone Patrick J.
Published: October 2004

Purpose

To determine whether voxel‐based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS).

Materials and Methods

We acquired GM MTR maps in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex‐ and age‐matched healthy controls. We evaluated the clinical status of the patients using the MS functional composite score and the expanded disability status scale. A two‐sample t‐test (P < 0.0001, k = 20, uncorrected for height threshold) was used to compare GM MTR maps from patients and controls on a voxel‐by‐voxel basis. We then extracted data from regions with t‐values above the statistical threshold to verify the significance of differences using a nonparametric Mann‐Whitney U‐test.

Results

A between‐groups comparison of GM maps revealed large abnormalities in the basal ganglia, including the bilateral thalamus, bilateral lenticular nucleus, bilateral head of caudate, and protuberance, and smaller abnormalities in the right insula, right BA 4, and left BA 40. The MTR measured in the left caudate and right insula was inversely correlated with duration following the first clinical event.

Conclusion

These results suggest that although MS is a multifocal demyelinating disease that affects white matter (WM), a pattern of tissue damage is present inside the GM involving predominantly basal ganglia at the earliest stage of the disease. J. Magn. Reson. Imaging 2004;20:765–771. © 2004 Wiley‐Liss, Inc.
Cross‐reactivity and clinical impact of the antibody response to hepatitis C virus second envelope glycoprotein (E2)
Authors: Hadlock Kenneth G. , Gish Robert , Rowe Judy , Rajyaguru Sonal S. , Newsom Margaret , Warford Ann , Foung Steven K.H.
Published: October 2004

The genotype of hepatitis C virus (HCV) can profoundly affect the success of antiviral therapy for HCV infection. A possible contributing factor is a varied immune response elicited by infection with different HCV genotypes. In this study, full‐length E2 proteins of HCV genotypes 1a, 1b, 2a, and 2b were used to determine the fraction of the humoral immune response to HCV E2 that is genotype specific. Greater than 90% of all infected individuals had serum antibodies to the four E2 proteins. Overall, individuals infected with genotype 1a or 1b were characterized by variable immune responses to HCV E2 with relatively high amounts of cross‐reactivity with other E2 proteins. Individuals infected with genotype 2a or 2b exhibited a strong preferential reactivity to genotype 2a and 2b E2 proteins. Individuals with elevated titers to HCV E2 were more likely to be infected with genotype 2a and had a significantly lower median viral load. These findings indicate that the antibody response to HCV E2 is affected by the genotype of the virus and that induction of a strong humoral immune response to HCV E2 may contribute to a decreased viral load. J. Med. Virol. 65:23–29, 2001. © 2001 Wiley‐Liss, Inc.
Japan‐specific subtype of hepatitis C virus genotype 1b, J subtype, has relatively low pathogenicity
Authors: Nakano Isao , Fukuda Yoshihide , Katano Yoshiaki , Toyoda Hidenori , Hayashi Kazuhiko , Kumada Takashi , Nakano Satoshi
Published: October 2004

The prognostic implication of viral genotype 1b for hepatitis C virus (HCV) infection has been controversial, possibly due to the pathogenetic heterogeneity of genotype 1b. We analyzed two newly delineated subtypes of HCV genotype 1b subtypes with respect to progression of liver disease. Patients with chronic HCV 1b infection (113 total, including 18 with chronic persistent hepatitis, 60 with chronic active hepatitis, 19 with cirrhosis, and 16 with hepatocellular carcinoma with cirrhosis) were studied to elucidate the factors associated with progression of liver disease. Factors evaluated included sex, age at diagnosis, blood transfusion history, and HCV genotype 1b subtype (W subtype or J subtype). W subtype was identified more often in association with chronic active hepatitis than with chronic persistent hepatitis (P = 0.0089), and more often in patients with cirrhosis than in those without (P = 0.0044). The age‐, sex‐, and transfusion history‐adjusted odds ratios with respect to histological activity and presence of cirrhosis for W subtype compared to J subtype were 6.966 (1.856 to 26.145) and 6.397 (1.506 to 27.179), respectively. Age at diagnosis was the most important risk factor for predicting development of cirrhosis and carcinoma. In conclusion, the W subtype of HCV 1b is associated closely with histologically active disease and development of cirrhosis, whereas the Japan‐specific J subtype has relatively low pathogenicity. HCV genotype 1b, therefore, is heterogeneous in its pathogenicity. J. Med. Virol. 65:45–51, 2001. © 2001 Wiley‐Liss, Inc.
Aciclovir selects for ganciclovir‐cross‐resistance of human cytomegalovirus in vitro that is only in part explained by known mutations in the UL97 protein*
Authors: Michel Detlef , Höhn Simone , Haller Tobias , Jun Dou , Mertens Thomas
Published: October 2004

Phenotypically, ganciclovir‐resistant human cytomegalovirus strains could be selected by aciclovir as effectively as by ganciclovir in vitro. Three clinical human cytomegalovirus isolates with different sensitivities against ganciclovir, aciclovir, foscarnet, and cidofovir, but without any mutation in the viral UL97 protein known to confer ganciclovir resistance, were propagated each in duplicate in the presence of ganciclovir or aciclovir. After drug selection, all 12 strains were less susceptible to ganciclovir (increase of 50% focus reduction dose between 2.1– and 31.5‐fold) but were still sensitive to foscarnet and cidofovir; 7/12 exhibited a ganciclovir‐resistant phenotype with a 50% focus reduction dose >30 μM, and in 6 out of these typical mutations in the UL97 coding region could be found by genotyping. All four strains selected from one isolate carried the identical UL97 mutation at amino acid position 460 (methionine to valine). The decreased sensitivity to ganciclovir and aciclovir in the other strains could neither be attributed to known UL97 mutations nor to mutations in the viral polymerase (UL54), which have been reported to induce resistance. J. Med. Virol. 65:70–76, 2001. © 2001 Wiley‐Liss, Inc.
Human cytomegalovirus a sequence and UL144 variability in strains from infected children
Authors: Bale James F. , Petheram Susan J. , Robertson Margaret , Murph Jody R. , Demmler Gail
Published: October 2004

Human cytomegalovirus (HCMV) displays genetic polymorphisms. This variability may contribute to strain‐specific tissue tropism and disease expression in HCMV‐infected humans. To determine strain variability in a sequence and UL144 gene regions, 51 low‐passage isolates from 44 HCMV‐infected children were studied. Isolates were obtained from 28 healthy children attending child care centers in Iowa and from 16 congenitally infected infants born in Texas. Isolates demonstrated substantial nucleotide variation in each gene region. Phylogenetic analysis of a sequence variability allowed 39 isolates to be grouped into six clades. The largest clade contained 16 isolates with ≥ 95% nucleotide homology. Forty‐eight of the 49 HCMV isolates yielding UL144 amplicons was grouped according to the clades described a few years ago [Lurain et al. (1999) Journal of Virology 73:10040–10050]. No linkage was observed among a sequence, UL144, and glycoprotein B (gB; UL55) polymorphisms. Four Texas and 11 Iowa isolates displayed ≥ 95% sequence homology for a sequence and UL144 regions and possessed identical gB genotypes. No relationship between UL144 polymorphisms and outcome of congenital HCMV infection was observed. These data indicate that HCMV strains circulating among young children have UL144 polymorphisms similar to those of HCMV strains excreted by immunocompromised adults. Identification of conserved nucleotide sequences among Iowa and Texas children suggests genetic stability and biologic importance of these gene regions. J. Med. Virol. 65:90–96, 2001. © 2001 Wiley‐Liss, Inc.
Molecular characterization of human enteroviruses in clinical samples: Comparison between VP2, VP1, and RNA polymerase regions using RT nested PCR assays and direct sequencing of products
Authors: Casas I. , Palacios G.F. , Trallero G. , Cisterna D. , Freire M.C. , Tenorio A.
Published: October 2004

Three nested RT‐PCR assays were developed to permit sensitive typing of enteroviruses directly from clinical samples. These assays amplified short fragments from different genomic regions codifying for three proteins: VP2, VP1, and RNA polymerase. Given that enteroviruses have a high rate of degeneration within target codons among serotypes, the primers used consisted of mixed base and deoxyinosine residues. These techniques detected at 0.03–0.003 TCID50 of prototype Poliovirus 1 and Echovirus 30. They were used to characterize the enteroviral RNA detected in 18 CSF, stool, and throw swab samples and in 8 enterovirus isolates from patients with several syndromes. Phylogenetic analysis in each independent sequenced region grouped the enterovirus into four clusters, enabling genetic classification. A comparative study was performed among the 26 sequences obtained after direct sequencing of products with those available in the nucleotide databases. The efficiency of each assay for enterovirus identification was evaluated by both distance (Clustal) and similarity (M‐NW) indices. Comparative results obtained independently in the three regions showed the highest yield of correlation between nucleotide sequences of all prototype serotypes and the analyzed genotypes in the VP1 region (26/26, 100% Clustal; 22/26, 85% M‐NW). Conversely, the VP2 region failed to identify some of the circulating enteroviruses (17/26, 65% Clustal; 16/26, 62% M‐NW). Using the RNA polymerase region, sequences from samples and isolates were associated with prototype strains whenever these were available (20/21, 95% Clustal; 12/21, 57% M‐NW). These assays were useful for molecular identification of enterovirus directly from samples even when isolation was not possible. J. Med. Virol. 65:138–148, 2001. © 2001 Wiley‐Liss, Inc.
Oral antibodies to human papillomavirus type 16 in women with cervical neoplasia
Authors: Marais Dianne J. , Best Jennifer M. , Rose Robert C. , Keating Patrick , Soeters Robbert , Denny Lynnette , Dehaeck Catherine M.C. , Nevin James , Kay Patti , Passmore Jo‐Ann , Williamson Anna‐Lise
Published: October 2004

This study investigated the relationship between human papillomavirus type 16 (HPV‐16) antibodies detected in oral fluid from women with cervical neoplasia, their HPV‐16 antibody seroprevalence, and their cervical HPV‐16 DNA presence. Cervical HPV‐16 DNA was detected by polymerase chain reaction in 43.2% (35/81) of these women. The prevalence of IgG and IgA antibodies to HPV‐16 virus‐like particles (VLP‐16) in oral fluid and was investigated by enzyme‐linked immunosorbent assay. Anti‐VLP‐16 IgA antibodies were detected in oral fluid from 54.3% (44/81) of women with cervical neoplasia, compared with 8% (3/36) in controls (P = 0.000002). Anti‐VLP‐16 IgG was detected in oral fluid from 43.2.9% (25/72) and 13.3% (4/30; P = 0.029), respectively. Women who were HPV‐16 DNA positive at their cervical lesion, displayed an oral fluid anti‐VLP‐16 IgA prevalence of 60.7% (17/28) and HPV‐16 DNA negative women an oral fluid anti‐VLP‐16 IgA prevalence of 50% (20/40; P = 0.38). Oral fluid anti‐VLP‐16 IgG prevalence in HPV‐16 DNA positive women was 28.6% (8/28) compared with 40% (16/40) in oral fluid from HPV‐16 DNA negative women (P = 0.3). Amongst HPV‐16 DNA positive women, the anti‐VLP‐16 IgG seroprevalence was 75% (21/28) and IgA seroprevalence 35.7% (10/28) and for the HPV‐16 DNA negative women these values were 60% (24/40) and 32.5% (13/40), respectively. Oral IgA antibody testing proved no more sensitive than serum antibody detection for the determination of HPV infection but could be useful as a non‐invasive screening method for women with cervical neoplasia and for estimating the mucosal antibody response to HPV vaccines. J. Med. Virol. 65:149–154, 2001. © 2001 Wiley‐Liss, Inc.
Modulation of expression of the MHC class I‐binding natural killer cell receptors, and NK activity in relation to viral load in HIV‐infected/AIDS patients
Authors: Ahmad Rasheed , Sindhu Sardar T.A.K. , Tran Phay , Toma Emil , Morisset Richard , Menezes José , Ahmad Ali
Published: October 2004

The natural killer (NK) cells play an important role in viral infections via their spontaneous cytolytic activity against virus‐infected cells as well as via secreting a variety of soluble mediators. The MHC class I‐binding NK receptors of these cells have emerged as the most important regulators of the effector activities of cytolytic cells (both NK and CTL). We have studied the modulation of NK activity and the expression of NK receptors in HIV‐infected/AIDS patients and report here that the NK activities of the patients with the lowest plasma HIV load were minimal and vice versa, suggesting a decrease in this activity following suppression of HIV replication. Interestingly, the NK activity correlated negatively with the peripheral blood CD4+ T‐cell counts of these patients. Furthermore, these patients showed decreased percentages of CD56+ cells expressing NK receptors of the immunoglobulin superfamily, whereas the percentages of CD8+ cells expressing these receptors were increased. Moreover, the expression of C‐type lectin‐like NK receptor‐associated invariant molecule CD94 was increased on CD8+ cells in these patients as compared with HIV‐seronegative controls. These changes in the expression of NK receptors were also evident within groups of these patients having different viral loads. These results show, for the first time, decreased innate immunity and changes in the expression of NK receptors on cytolytic cells in relation to viral burden in HIV‐infected/AIDS patient. J. Med. Virol. 65:431–440, 2001. © 2001 Wiley‐Liss, Inc.
Resistance profile and cross‐resistance of HIV‐1 among patients failing a non‐nucleoside reverse transcriptase inhibitor‐containing regimen*
Authors: Delaugerre C. , Rohban R. , Simon A. , Mouroux M. , Tricot C. , Agher R. , Huraux J.M. , Katlama C. , Calvez V.
Published: October 2004

The objectives were to determine the resistance profile and the rate of cross‐resistance in HIV‐1 infected patients failing an efavirenz or a nevirapine or a nevirapine then efavirenz containing regimens, and to investigate if zidovudine and more generally thymidine analog nucleosides lead to a particular genotypic pattern in nevirapine failing patients. A study was conducted in 104 patients with virological rebound to a non‐nucleoside reverse transcriptase inhibitors (NNRTI) regimen (efavirenz n = 39, nevirapine n = 46 and nevirapine then efavirenz n = 19). Genotypic resistance testing was carried out of detectable plasma HIV‐1 RNA (> 200 copies/ml). Among the 104 patients studied, only two patients failed to respond to the nevirapine regimen without selection of a NNRTI resistance mutation. All patients failing an efavirenz regimen harboured mutations conferring cross‐resistance to nevirapine (K103N, Y188L, G190S). Among patients failing the nevirapine regimen and presenting with NNRTI mutations, 35 (80%) harboured mutations conferring cross‐resistance to efavirenz (K101E, K103N, Y188L) and 9 (20%) harboured mutations conferring resistance to nevirapine alone (V106A and Y181C). In patients failing nevirapine then efavirenz therapy, all NNRTI resistance profile led to cross‐resistance to all available NNRTIs. Among patients receiving nevirapine, the selection of mutations associated with a cross‐resistance to efavirenz was more frequent statistically when a thymidine nucleoside analog (zidovudine or stavudine) was used in the regimen (P = 0.02). In conclusion, 100% of patients developed cross‐resistance to nevirapine and efavirenz after treatment by efavirenz and 80% after treatment by nevirapine. The use of a thymidine analog concomitantly with nevirapine leads to the preferential selection of cross‐resistance NNRTI mutations. J. Med. Virol. 65:445–448, 2001. © 2001 Wiley‐Liss, Inc.
Hepatitis B virus reactivation during cytotoxic chemotherapy‐enhanced viral replication precedes overt hepatitis
Authors: Yeo Winnie , Chan Paul K.S. , Chan Henry L.Y. , Mo Frankie K.F. , Johnson Philip J.
Published: October 2004

The diagnosis of HBV reactivation during cytotoxic chemotherapy is based on an abrupt rise in levels of serum HBV DNA in conjunction with a hepatitic picture and in the absence of other causes of hepatitis. However, several cases of “hepatitis” have been noted during chemotherapy in HBsAg‐positive patients, for which no cause could be found and in which HBV DNA levels were negative. One possible explanation is that HBV reactivation may, indeed, have been the cause but that HBV DNA levels became negative by the time ALT levels peaked and the clinical diagnosis of hepatitis was made. During the course of a longitudinal study of HBsAg‐seropositive cancer patients who were monitored during standard chemotherapy, the opportunity was available to test this hypothesis. J. Med. Virol. 65:473–477, 2001. © 2001 Wiley‐Liss, Inc.
Molecular cloning and expression of woodchuck granulocyte‐macrophage colony stimulating factor*
Authors: Wu Hui‐Lin , Chen Pei‐Jer , Lin Hua‐Kuo , Lee Ren‐Shiang , Lin Hsiu‐Lin , Liu Chun‐Jen , Lee Pi‐Jen , Lee Jihjong J. , Chen Ding‐Shinn
Published: October 2004

Granulocyte‐macrophage colony stimulating factor (GM‐CSF) has immunoregulatory and antiviral effects, and may thus be promising for the treatment of chronic hepatitis B. Using woodchuck hepatitis virus (WHV)‐infected woodchuck as an animal model to test the efficacy and safety of GM‐CSF on the therapy of chronic hepatitis B, woodchuck GM‐CSF will be required due to the apparent species‐specific activity of GM‐CSF. The cDNA of woodchuck GM‐CSF was cloned using reverse transcription‐polymerase chain reaction (RT‐PCR) with primers deriving from highly conserved regions of GM‐CSF genes from other species. The deduced amino acids, including the signal peptide, is 138 in length and its identities to human, murine, canine and bovine GM‐CSFs are 63, 49, 63, and 63% respectively. The genomic DNA of woodchuck GM‐CSF was also cloned by PCR. Its organization is highly homologous to that of human and murine GM‐CSF genes, consisting of four exons and three introns. Cloned woodchuck GM‐CSF was expressed transiently in 293T cells. The recombinant protein expressed was found to stimulate the growth and differentiation of woodchuck bone marrow cells, indicating the protein expressed by the cloned gene is functional. These results pave the way for future studies on the potential role of GM‐CSF for the treatment of chronic hepatitis B by using this animal model. J. Med. Virol. 65:567–575, 2001. © 2001 Wiley‐Liss, Inc.
Human herpesvirus 6 downregulates major histocompatibility complex class I in dendritic cells
Authors: Hirata Yuko , Kondo Kazuhiro , Yamanishi Koichi
Published: October 2004

The expression of major histocompatibility complex (MHC) class I, class II, CD1a, and CD 83 in dendritic cells (DCs) after infection with human herpesvirus 6 (HHV‐6) was examined. Whereas there was no significant change in the expression of CD1a, CD83, and MHC class II in infected DCs, MHC class I expression was downregulated after infection with HHV‐6 variant A but not HHV‐6B. The expression of HHV‐6 immediate‐early or early genes was required for the downregulation of MHC class I. The de novo synthesis of MHC class I was greatly suppressed by infection with HHV‐6A in DCs, while its rate of degradation was only slightly elevated. These results suggest that HHV‐6A may escape from the host immune system in DCs by causing the downregulation of MHC class I synthesis. J. Med. Virol. 65:576–583, 2001. © 2001 Wiley‐Liss, Inc.
Quantitative study of the infection in brain neurons in human rabies
Authors: Jackson Alan C. , Ye Hongtao , Ridaura‐Sanz Cecilia , Lopez‐Corella Eduardo
Published: October 2004

Rabies virus is a highly neuronotropic virus that causes encephalomyelitis. Rabies virus infection was studied in neurons in the brain of an 8‐year‐old girl that died of rabies in Mexico. The extent of the neuronal infection was evaluated quantitatively in neuronal cell types of the brain using histologic staining for Negri bodies and immunoperoxidase staining for rabies virus antigen in the same neurons. Quantitative image analysis was used to compare the amount of infection in five different neuronal cell types, which was expressed as a percentage of neuronal area. Purkinje cells and periaqueductal gray neurons showed the largest percentage area for both Negri bodies and signal for rabies virus antigen. In general, there was a good linear relationship between the area of Negri bodies and the area of signal for rabies virus antigen. Many neurons with rabies virus antigen did not have Negri bodies, however, and some neurons with large antigen signals, especially Purkinje cells and periaqueductal gray neurons, lacked Negri bodies. Formation of Negri bodies is likely influenced by factors that vary in different neuronal cell types. J. Med. Virol. 65:614–618, 2001. © 2001 Wiley‐Liss, Inc.