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Drachmann's regularization approach is implemented for floating explicitly correlated Gaussians (fECGs) and molecular systems. Earlier applications of drachmannized relativistic corrections for molecular systems were hindered due to the unknown analytic matrix elements of 1/rix1/rjy-type operators with fECGs. In the present work, one of the 1/r factors is approximated by a linear combination of Gaussians, which results in calculable integrals. The numerical approach is found to be precise and robust over a range of molecular systems and nuclear configurations, and thus, it opens the route toward an automated evaluation of high-precision relativistic corrections over potential energy surfaces of polyatomic systems. Furthermore, the newly developed integration approach makes it possible to construct the matrix representation of the square of the electronic Hamiltonian relevant for energy lower-bound as well as time-dependent computations of molecular systems with a flexible and high-precision fECG basis representation., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

The aim of this study was to investigate the transition from non-covalent reversible over covalent reversible to covalent irreversible inhibition of cysteine proteases by making delicate structural changes to the warhead scaffold. To this end, dipeptidic rhodesain inhibitors with different N -terminal electrophilic arenes as warheads relying on the S N Ar mechanism were synthesized and investigated. Strong structure-activity relationships of the inhibition potency, the degree of covalency, and the reversibility of binding on the arene substitution pattern were found. The studies were complemented and substantiated by molecular docking and quantum-mechanical calculations of model systems. Furthermore, the improvement in the membrane permeability of peptide esters in comparison to their corresponding carboxylic acids was exemplified.

Interactions in atomic and molecular systems are dominated by electromagnetic forces and the theoretical framework must be in the quantum regime. The physical theory for the combination of quantum mechanics and electromagnetism, quantum electrodynamics has been "established" by the mid-twentieth century, primarily as a scattering theory. To describe atoms and molecules, it is important to consider bound states. In the nonrelativistic quantum mechanics framework, bound states can be efficiently computed using robust and general methodologies with systematic approximations developed for solving wave equations . With the sight of the development of a computational quantum electrodynamics framework for atomic and molecular matter, the field theoretic Bethe-Salpeter wave equation expressed in space-time coordinates, its exact equal-time variant, and emergence of a relativistic wave equation, is reviewed. A computational framework, with initial applications and future challenges in relation with precision spectroscopy, is also highlighted., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

A general computational scheme for the (nonrelativistic) Bethe logarithm is developed, opening the route to "routine" evaluation of the leading-order quantum electrodynamics correction (QED) relevant for spectroscopic applications for small polyatomic and polyelectronic molecular systems. The implementation relies on the Schwartz method and minimization of a Hylleraas functional. In relation with electronically excited states, a projection technique is considered, which ensures positive definiteness of the functional over the entire parameter (photon momentum) range. Using this implementation, the Bethe logarithm is converged to a relative precision better than 1:10 3 for selected electronic states of the two-electron H 2 and H 3 + , and the three-electron He 2 + and H+H 2 molecular systems. The present work focuses on nuclear configurations near the local minimum of the potential energy surface, but the computations can be repeated also for other structures.

Variational and perturbative relativistic energies are computed and compared for two-electron atoms and molecules with low nuclear charge numbers. In general, good agreement of the two approaches is observed. Remaining deviations can be attributed to higher-order relativistic, also called non-radiative quantum electrodynamics (QED), corrections of the perturbative approach that are automatically included in the variational solution of the no-pair Dirac-Coulomb-Breit (DCB) equation to all orders of the α fine-structure constant. The analysis of the polynomial α dependence of the DCB energy makes it possible to determine the leading-order relativistic correction to the non-relativistic energy to high precision without regularization. Contributions from the Breit-Pauli Hamiltonian, for which expectation values converge slowly due the singular terms, are implicitly included in the variational procedure. The α dependence of the no-pair DCB energy shows that the higher-order (α 4 E h ) non-radiative QED correction is 5% of the leading-order (α 3 E h ) non-radiative QED correction for Z = 2 (He), but it is 40% already for Z = 4 (Be 2+ ), which indicates that resummation provided by the variational procedure is important already for intermediate nuclear charge numbers.

The Breit interaction is implemented in the no-pair variational Dirac-Coulomb (DC) framework using an explicitly correlated Gaussian basis reported in the previous paper [P. Jeszenszki, D. Ferenc, and E. Mátyus, J. Chem. Phys. 156, 084111 (2022)]. Both a perturbative and a fully variational inclusion of the Breit term are considered. The no-pair DC plus perturbative Breit and the no-pair DC-Breit energies are compared with perturbation theory results including the Breit-Pauli Hamiltonian and leading-order non-radiative quantum electrodynamics corrections for low Z values. Possible reasons for the observed deviations are discussed.

The Dirac-Coulomb equation with positive-energy projection is solved using explicitly correlated Gaussian functions. The algorithm and computational procedure aims for a parts-per-billion convergence of the energy to provide a starting point for further comparison and further developments in relation with high-resolution atomic and molecular spectroscopy. Besides a detailed discussion of the implementation of the fundamental spinor structure, permutation, and point-group symmetries, various options for the positive-energy projection procedure are presented. The no-pair Dirac-Coulomb energy converged to a parts-per-billion precision is compared with perturbative results for atomic and molecular systems with small nuclear charge numbers. Paper II [D. Ferenc, P. Jeszenszki, and E. Mátyus, J. Chem. Phys. 156, 084110 (2022).] describes the implementation of the Breit interaction in this framework.

The quantum harmonic model and the two-phase thermodynamic method (2PT) are widely used to obtain quantum-corrected properties such as isobaric heat capacities or molar entropies. 2PT heat capacities were calculated inconsistently in the literature. For water, the classical heat capacity was also considered, but for organic liquids, it was omitted. We reanalyzed the performance of different quantum corrections on the heat capacities of common organic solvents against experimental data. We have pointed out serious flaws in previous 2PT studies. The vibrational density of states was calculated incorrectly causing a 39% relative error in diffusion coefficients and 45% error in the 2PT heat capacities. The wrong conversion of isobaric and isochoric heat capacities also caused about 40% error but in the other direction. We have introduced the concept of anharmonic correction (AC), which is simply the deviation of the classical heat capacity from that of the harmonic oscillator model. This anharmonic contribution is around +30 to 40 J/(mol K) for water depending on the water model and -8 to -10 J/(mol K) for hydrocarbons and halocarbons. AC is unrealistically large, +40 J/(K mol) for alcohols and amines, indicating some deficiency of the OPLS force field. The accuracy of the computations was also assessed with the determination of the self-diffusion coefficients.

A variational solution procedure is reported for the many-particle no-pair Dirac-Coulomb and Dirac-Coulomb-Breit Hamiltonians aiming at a parts-per-billion (ppb) convergence of the atomic and molecular energies, described within the fixed nuclei approximation. The procedure is tested for nuclear charge numbers from Z = 1 (hydrogen) to 28 (iron). Already for the lowest Z values, a significant difference is observed from leading-order Foldy-Woythusen perturbation theory, but the observed deviations are smaller than the estimated self-energy and vacuum polarization corrections.

Objectives: This study aims to compare the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) with other commonly utilized modalities., Materials and Methods: The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with that of other modalities. Studies were classified into 10 categories as follows: (1) open flap debridement (OFD) alone versus OFD/PRF; (2) OFD/bone graft (OFD/BG) versus OFD/PRF; (3) OFD/BG versus OFD/BG/PRF; (4-6) OFD/barrier membrane (BM), OFD/PRP, or OFD/enamel matrix derivative (EMD) versus OFD/PRF; (7) OFD/EMD versus OFD/EMD/PRF; (8-10) OFD/PRF versus OFD/PRF/metformin, OFD/PRF/bisphosphonates, or OFD/PRF/statins. Weighted means and forest plots were calculated for probing depth (PD), clinical attachment level (CAL), and radiographic bone fill (RBF)., Results: From 551 articles identified, 27 RCTs were included. The use of OFD/PRF statistically significantly reduced PD and improved CAL and RBF when compared to OFD. No clinically significant differences were reported when OFD/BG was compared to OFD/PRF. The addition of PRF to OFD/BG led to significant improvements in CAL and RBF. No differences were reported between any of the following groups (OFD/BM, OFD/PRP, and OFD/EMD) when compared to OFD/PRF. No improvements were also reported when PRF was added to OFD/EMD. The addition of all three of the following biomolecules (metformin, bisphosphonates, and statins) to OFD/PRF led to statistically significant improvements of PD, CAL, and RBF., Conclusions: The use of PRF significantly improved clinical outcomes in intrabony defects when compared to OFD alone with similar levels being observed between OFD/BG and OFD/PRF. Future research geared toward better understanding potential ways to enhance the regenerative properties of PRF with various small biomolecules may prove valuable for future clinical applications. Future research investigating PRF at histological level is also needed., Clinical Relevance: The use of PRF in conjunction with OFD statistically significantly improved PD, CAL, and RBF values, yielding to comparable outcomes to OFD/BG. The combination of PRF with bone grafts or small biomolecules may offer certain clinical advantages, thus warranting further investigations.

Di- tert -butyl oxymethyl phosphonates were investigated regarding their suitability for preparing the active pharmaceutical ingredient tenofovir (PMPA). First, an efficient and simple access to the crystalline di- tert -butyl(hydroxymethyl)phosphonate was developed. O-Mesylation gave high yields of the active phosphonomethylation reagent. For the synthesis of tenofovir, a two-step sequence was developed using Mg(O t Bu) 2 as the base for the alkylation of ( R )-9-(2-hydroxypropyl)adenine. Subsequent deprotection could be achieved with aqueous acids. (Di- tert -butoxyphosphoryl)methyl methanesulfonate showed to be the most efficient electrophile tested, affording PMPA in 72% yield on a 5 g scale. The developed protocol could also be applied for the preparation of the hepatitis B drug adefovir (64% yield/1 g scale)., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

The rovibrational intervals of the ^{4}He_{2}^{+} molecular ion in its X ^{2}Σ_{u}^{+} ground electronic state are computed by including the nonadiabatic, relativistic, and leading-order quantum-electrodynamics corrections. Good agreement of theory and experiment is observed for the rotational excitation series of the vibrational ground state and the fundamental vibration. The lowest-energy rotational interval is computed to be 70.937 69(10)  cm^{-1} in agreement with the most recently reported experimental value, 70.937 589(23)(60)_{sys}  cm^{-1} [L. Semeria et al., Phys. Rev. Lett. 124, 213001 (2020)PRLTAO0031-900710.1103/PhysRevLett.124.213001].

Nuclear quantum effects have significant contributions to thermodynamic quantities and structural properties; furthermore, very expensive methods are necessary for their accurate computation. In most calculations, these effects, for instance, zero-point energies, are simply neglected or only taken into account within the quantum harmonic oscillator approximation. Herein, we present a new method, Generalized Smoothed Trajectory Analysis, to determine nuclear quantum effects from molecular dynamics simulations. The broad applicability is demonstrated with the examples of a harmonic oscillator and different states of water. Ab initio molecular dynamics simulations have been performed for ideal gas up to the temperature of 5000 K. Classical molecular dynamics have been carried out for hexagonal ice, liquid water, and vapor at atmospheric pressure. With respect to the experimental heat capacity, our method outperforms previous calculations in the literature in a wide temperature range at lower computational cost than other alternatives. Dynamic and structural nuclear quantum effects of water are also discussed.

The mass-correction function is evaluated for selected excited states of the hydrogen molecule within a single-state nonadiabatic treatment. Its qualitative features are studied at the avoided crossing of the EF with the GK state and also for the outer well of the HH¯ state. For the HH¯ state, a negative mass correction is obtained for the vibrational motion near the outer minimum, which accounts for most of the deviation between experiment and earlier theoretical work.

A fully regio- and diastereoselective electrochemical 4a-2'-coupling of a 3',4',5'-trioxygenated laudanosine derivative enables the synthesis of the corresponding morphinandienone. This key intermediate is further transformed into (-)-oxycodone through conjugate nucleophilic substitution for E-ring closure and [4 + 2] cycloaddition with photogenerated singlet oxygen to accomplish diastereoselective hydroxylation at C-14. The anodic transformation provides high yields and can be performed under constant current conditions both in a simple undivided cell or in continuous flow.

The biosynthesis of thebaine is based on the regioselective, intramolecular, oxidative coupling of (R)-reticuline. For decades, chemists have sought to mimic this coupling by using stoichiometric oxidants. However, all approaches to date have suffered from low yields or the formation of undesired regioisomers. Electrochemistry would represent a sustainable alternative in this respect but all attempts to accomplish an electrochemical synthesis of thebaine have failed so far. Herein, a regio- and diastereoselective anodic coupling of 3',4',5'-trioxygenated laudanosine derivatives is presented, which finally enables electrochemical access to (-)-thebaine., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Serum albumin has been identified as an endogenous protein that is integral to early bone regeneration. We hypothesized that albumin addition to allografts may result in better bone remodeling than what can be achieved with anorganic xenografts. Sinus elevations were performed at 32 sites of 18 patients with the lateral window technique. Sites either received filling with an anorganic bovine bone mineral (ABBM, BioOss, Geistlich, CH) or albumin impregnated allograft (BoneAlbumin, OrthoSera, AT). After 6-months patients received dental implants and 16 bone core biopsy samples were obtained from the ABBM filled, and 16 from the BoneAlbumin augmented sites. The biopsies were examined by histomorphometry and µCT. Percentage of the residual graft in the BoneAlbumin group was 0-12.7%, median 5.4% vs. ABBM 6.3-35.9%, median 16.9%, p < 0.05. Results of the µCT analysis showed that the microarchitecture of the augmented bone in the BoneAlbumin group resembles that of the native maxilla in morphometric parameters Trabecular Pattern Factor and Connectivity. Our data show that while ABBM successfully integrates into the newly formed bone tissue as persisting particles, BoneAlbumin is underway towards complete remodeling with new bone closely resembling that of the intact maxilla., Competing Interests: Author Lacza Zsombo is an inventor on a patent covering albumin coating and holds stock in OrthoSera GmbH, a startup that is commercializing the technology. All other authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Two consecutive Cu-catalyzed Ullmann-type C-O couplings permitted the first successful entry toward the curare alkaloids (±)-tubocurine and (±)-curine. Starting from vanillin, the synthetic sequence comprises 15 linear steps and includes a total of 24 transformations. In addition, the total synthesis of tubocurine represents a formal total synthesis of the famous arrow poison alkaloid tubocurarine.

Functional mimetics of the sialyl Lewis(X) tetrasaccharide were prepared by the enzymatic sialylation of a 1,3-diglycosylated indole and a glycosyl azide, which was subsequently transformed into a 1,4-diglycosylated 1,2,3-triazole, by using the trans-sialidase of Trypanosoma cruzi. These compounds inhibited the binding of E-, L-, and P-selectin-coated nanoparticles to polyacrylamide-bound sialyl-Lewis(X) -containing neighboring sulfated tyrosine residues (sTyr/sLe(X) -PAA) at low or sub-millimolar concentrations. Except for E-selectin, the mimetics showed higher activities than the natural tetrasaccharide., (© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.)

The cyclocondensation of enones with aminoacetonitrile furnishes 3,4-dihydro-2H-pyrrole-2-carbonitriles which can be readily converted to 2,4-disubstituted pyrroles by microwave-induced dehydrocyanation. Alternatively, oxidation of the intermediates produces 3,5-disubstituted pyrrole-2-carbonitriles.

The asymmetric unit of the title compound, C(11)H(9)N(3)O, contains two independent and nearly identical mol-ecules (A and B). Mol-ecule A can be transformed to B using a rotation of approximately 85° around the [111] direction. Each A mol-ecule is connected to three B mol-ecules via N-H⋯N and N-H⋯O hydrogen bonds and vice versa. Centrosymmetric-ally related mol-ecules of the same residue form π-π inter-actions with centroid-centroid distances of 4.326 (1) and 3.826 (1) Å for the benzene rings of mol-ecules A and B, respectively.

The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.

One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 giga-electron volts. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 giga-electron volts, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.

The atmospheric Cherenkov gamma-ray telescope MAGIC, designed for a low-energy threshold, has detected very-high-energy gamma rays from a giant flare of the distant Quasi-Stellar Radio Source (in short: radio quasar) 3C 279, at a distance of more than 5 billion light-years (a redshift of 0.536). No quasar has been observed previously in very-high-energy gamma radiation, and this is also the most distant object detected emitting gamma rays above 50 gigaelectron volts. Because high-energy gamma rays may be stopped by interacting with the diffuse background light in the universe, the observations by MAGIC imply a low amount for such light, consistent with that known from galaxy counts.

Alpha-Aminonitriles derived from 2-aminocinnamic acid esters and amides can be cyclized under basic conditions to furnish substituted indole-3-acetic acid derivatives in quantitative yield. The reaction provides a simple access to a class of biologically active compounds.

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.

We have previously reported the potent in vitro HIV-1 anti-reverse transcriptase activity of a 35-mer of 4-thio-deoxyuridylate [(s(4)dU)(35)]. In efforts to define its activity in a more physiological system, studies were carried out to determine the stage of viral infection that this compound mediates its anti-viral effect. Results of the studies reported herein show that (s(4)dU)(35) is nontoxic and is capable of inhibiting both single and multi-drug resistant HIV strains (IC(50): 0.8-25.4 microg/ml) in vitro. Besides its previously reported anti-RT activity, (s(4)dU)(35) mediated its antiviral action by preventing virus attachment (IC(50): 0.002-0.003 microg/ml), and was stable in vitro and slowly degraded by DNAses. Competition studies and fluorescence resonance energy transfer (FRET) experiments indicated that (s(4)dU)(35) preferentially binds to CD4 receptors, but not to CD48. Confocal laser scanning microscopy (CLSM) studies showed that (s(4)dU)(35) did not penetrate into the cells and colocalized with cell surface thioredoxin. Our studies identify (s(4)dU)(35) as a potential novel HIV entry inhibitor that may have utility as either a systemic antiretroviral or as a preventing agent for HIV transmission.

The reaction of 2-carboxybenzaldehyde with primary amines in the presence of cyanide leads to the formation of 2-substituted amino(3-oxo-2,3-dihydro-1H-isoindol-1-ylidene)acetonitriles. These compounds originate from the condensation of 2-carboxybenzaldehyde with the amine and two molecules of hydrogen cyanide and represent a novel class of isoindolinones.

The role of A/G polymorphism at nucleotide -1082 in the interleukin-10 (IL-10) promoter was assessed by following the disease course of 253 patients who had had a routine diagnostic Hybrid Capture human papillomavirus (HPV) test because of cytologic or colposcopic abnormalities of the uterine cervix. At baseline, 97 (78%) of the 125 high-risk HPV-positive and 83 (65%) of the 128 HPV-negative patients had equivocal cytologic atypia classified as P3 by the Papanicolaou classification, and the rest of the patients had mild colposcopic atypia with cytologic results of no oncogenic significance. In the high-risk HPV-infected patients, the frequency distribution of the nt -1082 genotypes (A/A: 28%; A/G: 52%; G/G: 20%) did not differ significantly from that in the controls (A/A: 25%; A/G: 51%; G/G: 24%; p = 0.70). On the other hand, the nt -1082 G allele tended to decrease susceptibility to equivocal cytologic atypia unrelated to HPV infection (A/G: OR = 0.56 [95% CI: 0.31-1.02], G/G: OR = 0.27 [95% CI: 0.11-0.63], p for trend = 0.05). With respect to the development of high-grade cervical intraepithelial neoplasia (CIN), the established risk factors, such as high-risk HPV infection (RR = 104.6, 95% CI: 14.2-769.9) and cytologic atypia (RR = 9.6, 95% CI: 2.34-39.7) but not the various nt -1082 genotypes (A/A: reference; A/G: RR = 1.11 [95% CI: 0.59-2.08]; G/G: RR = 0.62 [95% CI: 0.25-1.50]) were found to increase the risk for high-grade CIN. In conclusion, the nt -1082 polymorphism had no influence on the early phase of cervical carcinogenesis but may determine different susceptibilities to cervical abnormalities unrelated to HPV infection.

Authors studied the effect of highly active antiretroviral therapy (HAART) on balance of the antibodies that enhance or neutralize growth of HIV-1(IIIB) strain in MT-4 cells in the presence or absence of human complement. Sequential serum samples were collected from 28 patients in advanced stage of HIV disease before and during HAART. The balance of the enhancing and neutralizing antibodies was expressed by an index value (E/N I). Samples with an E/N I of <0.5 (twofold decrease in virus production) were considered as neutralizing, whereas samples with an E/N I>2.0 (twofold increase in virus production) were considered as enhancing. At the beginning of HAART serum samples from eight patients enhanced, and samples from only two patients neutralized the virus in the presence of complement, median (25th-75th percentile) value of E/N I was 1.32 (0.79-2.29). E/N I significantly (P<0.0001) dropped to 0.37 (0.19-0.57) during the follow-up period of 18.5 (10.5-23.5) months under HAART. Similar changes were detected when serum samples were tested with no complement added. The E/N I values were also markedly decreased when cultures inoculated with mixtures of HIV and purified IgG prepared from serum pools taken before and during HAART, respectively, were compared. In the last samples of 20/28 patients, neutralization was measured even in the presence of complement while enhancement was found with none of these samples. These findings suggest that HAART results in disappearance of enhancing antibodies and switches the E/N I toward neutralization.

Replication of human cytomegalovirus (HCMV) was investigated in various T-cell lines expressing the tax gene product of human T-cell leukemia-lymphoma virus type I (HTLV-I). Differential patterns of HCMV replication were found in HTLV-I-carrying cell lines. HCMV gene expression was restricted to the immediate-early genes in MT-2 and MT-4 cells, whereas full replication cycle of the virus was observed in C8166-45 cells. Productive HCMV infection induced a cytopathic effect resulting in the lysis of infected cells. The results of electrophoretic mobility shift assay (EMSA) showed high levels of NF-kappaB-, CREB/ATF-1-, and SRF-specific DNA binding activity in all Tax-positive cell lines. In contrast, SP1 activity could be detected only in C8166-45 cells. Using an inducible system (Jurkat cell line JPX-9), a dramatic increase in NF-kappaB, CREB/ATF-1, SRF, and SP1 binding activity, as well as productive HCMV infection, were observed upon Tax expression. Overexpression of SP1 in MT-2 and MT-4 cells converted HCMV infection from an abortive to a productive one. These data suggest that the stimulatory effect of Tax protein on HCMV in T cells is accomplished through at least five host-related transcription factor pathways. The results of this study provide possible mechanisms whereby HCMV infections might imply suppression of adult T-cell leukemia., (Copyright 2003 Wiley-Liss, Inc.)

Human herpesvirus 6 (HHV-6) and human immunodeficiency virus type 1 (HIV-1) may interact during transplacental transmission of HIV-1. The placental syncytiotrophoblast layer serves as the first line of defense of the fetus against viruses. Patterns of replication of HHV-6 variant A (HHV-6A) and HIV-1 were analyzed in singly and dually infected human term syncytiotrophoblast cells cultured in vitro. For this purpose, the GS strain of HHV-6A and the Ba-L and IIIB strains of HIV-1 were used. HHV-6A replication was restricted at the level of early gene products in singly infected syncytiotrophoblasts, whereas no viral protein expression was found in cells infected with HIV-1 alone. Coinfection of syncytiotrophoblast cells with HHV-6A and HIV-1 resulted in production of infectious HIV-1. In contrast, no enhancement of HHV-6A expression was observed in cell cultures infected with both viruses. Uninfected syncytiotrophoblast cells were found to express CXCR4 and CCR3 but not CD4 or CCR5 receptors. Infection of syncytiotrophoblasts with HHV-6A did not induce CD4 expression and had no influence on chemokine receptor expression. Activation of HIV-1 from latency in coinfected cells was mediated by the immediate-early (IE)-A and IE-B gene products of HHV-6A. Open reading frames U86 and U89 of the IE-A region were able to activate HIV-1 replication in a synergistic manner. The data suggest that in vivo double infection of syncytiotrophoblast cells with HHV-6A and HIV-1 could contribute to the transplacental transmission of HIV-1 but not HHV-6A., (Copyright 2002 Wiley-Liss, Inc.)

Two-particle interferometry of positive kaons is studied in Pb+Pb collisions at mean transverse momenta approximately 0.25 and 0.91 GeV/c. A three-dimensional analysis was applied to the lower p(T) data, while a two-dimensional analysis was used for the higher p(T) data. We find that the source-size parameters are consistent with the m(T) scaling curve observed in pion-correlation measurements in the same collisions, and that the duration time of kaon emission is consistent with zero within the experimental sensitivity.

We present the first measurement of fluctuations from event to event in the production of strange particles in collisions of heavy nuclei. The ratio of charged kaons to charged pions is determined for individual central Pb+Pb collisions. After accounting for the fluctuations due to detector resolution and finite number statistics we derive an upper limit on genuine nonstatistical fluctuations, which could be related to a first- or second-order QCD phase transition. Such fluctuations are shown to be very small.

Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at square root(S)NN = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.

The invariant cross section as a function of transverse momentum for antideuterons produced in 158A GeV/c per nucleon Pb+Pb central collisions has been measured by the NA44 experiment at CERN. This measurement, together with a measurement of antiprotons, allows for the determination of the antideuteron coalescence parameter. The extracted coalescence radius is found to agree with the deuteron coalescence radius and radii determined from two particle correlations.

In humans the HIV infection results in a chronic disease with a permanent fight between factors controlling HIV and the escape of the virus. Fromthese control mechanisms the present review summarizes the role betwen complement and autoantibodies; the competition of complement and anti-HIV antibodies for binding sites, the role of mannan-binding lectin in the susceptibility to and in the survival after HIV infection, the contribution of complement-dependent enhancing type antibodies to the clinical progression of HIV disease as well as the changing pattern of some autoantibodies (mimicking MHC class II molecules, anti-heat shock protein 60 antibodies and anti-C1q antibodies) which were found to correlate to immunological and clinical parameters.

The sera of 173 haemodialysis patients treated in two dialysis centers in Hungary were tested for the presence of HIV (HTLV III/LAV) antibodies. Four different commercial enzyme immunoassay (EIA) kits and two types (CEM/LAV, and H9/HTLV III) of indirect immunofluorescence assay (IFA) were used. The Western blot technique was applied as confirmatory test in the study. No confirmed positive results were found in any of the cases. However, in 15 patients (8.7%) false positive (not confirmable by the Western blot assay) results were obtained in at least one but mostly in all of the three type 1 EIA kits (ORGANON, ELECTRONUCLEONICS, SORIN) applied. In 4 patients, the IFA assay also gave false positive results which could be repeated in sequential samples taken from the same patients. Increased reactivity in the control plate (coated with a concentrate of cellular material shed by uninfected H9 cell line) of the SORIN kit was found only in a few false positive samples and no fluorescence with the uninfected H9 or CEM cells was observed in any of the sera showing a false positive IFA. These results indicate that the false positive anti-HIV results frequently observable in haemodialysis patients are not simply the consequence of the presence of antibodies reacting with the uninfected H9 and/or CEM cells but they are most probably due to antibodies against antigens expressed on these cells only after infection with the human immunodeficiency virus.