bluuebunny/crossref_metadata_2025 huggingface dataset:
QUANTUM EFFECTS AND SUPERQUINTESSENCE IN THE NEW AGE OF PRECISION COSMOLOGY
Authors: GUNZIG E. , SAA ALBERTO
Published: February 2005

Recent observations of Type Ia supernova at high redshifts establish that the dark energy component of the universe has (a probably constant) ratio between pressure and energy density [Formula: see text]. The conventional quintessence models for dark energy are restricted to the range -1≤w<0, with the cosmological constant corresponding to w=-1. Conformally coupled quintessence models are the simplest ones compatible with the marginally allowed superaccelerated regime (w<-1). However, they are known to be plagued with anisotropic singularities.

We argue here that the extension of the classical approach to the semiclassical one, with the inclusion of quantum counterterms necessary to ensure the renormalization, can eliminate the anisotropic singularities preserving the isotropic behavior of conformally coupled superquintessence models. Hence, besides of having other interesting properties, they are consistent candidates to describe the superaccelerated phases of the universe compatible with the present experimental data.
THE NATURE OF GRAVITATIONAL SINGULARITIES
Authors: GARFINKLE DAVID
Published: February 2005

The nature of gravitational singularities, long mysterious, has now become clear through a combination of mathematical and numerical analysis. As the singularity is approached, the time derivative terms in the field equations dominate, and the singularity behaves locally like a homogeneous oscillatory spacetime.
TOWARDS A FUTURE SINGULARITY?
Authors: GASPERINI M.
Published: February 2005

We discuss whether the future extrapolation of the present cosmological state may lead to a singularity even in case of "conventional" (negative) pressure of the dark energy field, namely w=p/ρ≥-1. The discussion is based on an often neglected aspect of scalar–tensor models of gravity: the fact that different test particles may follow the geodesics of different metric frames, and the need for a frame-independent regularization of curvature singularities.
DARK GEOMETRY
Authors: CEMBRANOS J. A. R. , DOBADO A. , MAROTO A. L.
Published: February 2005

Extra-dimensional theories contain additional degrees of freedom related to the geometry of the extra space which can be interpreted as new particles. Such theories allow to reformulate most of the fundamental problems of physics from a completely different point of view. In this essay, we concentrate on the brane fluctuations which are present in brane-worlds, and how such oscillations of the own space–time geometry along curved extra dimensions can help to resolve the Universe missing mass problem. The energy scales involved in these models are low compared to the Planck scale, and this means that some of the brane fluctuations distinctive signals could be detected in future colliders and in direct or indirect dark matter searches.
QUANTUM NATURE OF BLACK HOLES
Authors: HELFER ADAM D.
Published: February 2005

I reconsider Hawking's analysis of the effects of gravitational collapse on quantum fields, taking into account interactions between the fields. The ultra-high energy vacuum fluctuations, which had been considered to be an awkward peripheral feature of the analysis, are shown to play a key role. By interactions, they can scatter particles to, or create pairs of particle at, ultra-high energies. The energies rapidly become so great that quantum gravity must play a dominant role. Thus the vicinities of black holes are essentially quantum-gravitational regimes.
NO BLACK HOLE INFORMATION PUZZLE IN A RELATIONAL UNIVERSE
Authors: GAMBINI RODOLFO , PORTO RAFAEL A. , PULLIN JORGE
Published: February 2005

The introduction of a relational time in quantum gravity naturally implies that pure quantum states evolve into mixed quantum states. We show, using a recently proposed concrete implementation, that the rate at which pure states naturally evolve into mixed ones is faster than that due to collapsing into a black hole that later evaporates. This is rather remarkable since the fundamental mechanism for decoherence is usually very weak. Therefore the "black hole information puzzle" is rendered de-facto unobservable.
GRAVITO-ELECTROMAGNETISM: GLIMPSES OF UNEXPLORED DEEP CONNECTIONS
Authors: UNNIKRISHNAN C. S. , GILLIES G. T.
Published: February 2005

Any attempt at unification of the fundamental interactions will recognize its 'right path' when electromagnetism and gravity are seen together as manifestations of the same interaction. First excitement along this direction was the Kaluza–Klein program, and the unsuccessful attempt was Einstein's unified field theory. Over the years, the program has changed much, but the basic idea that there are links between gravity and electromagnetism, perhaps in a higher dimensional world, has not changed. There are several interesting and important phenomenological aspects related to this issue, to be experimentally explored at the classical level, which may reveal some of the deep connections between the two long range interactions. In this essay, we discuss a program to experimentally explore some connections between gravity and electromagnetism, not yet adequately studied. Some of the key issues we address are the complete absence of gravity for electrons inside a metal drift tube (Schiff–Barnhill effect) and its rotational variant, the Schuster–Blackett relation between rotation of neutral matter and generation of magnetic fields, and a variation of the Faraday unipolar induction. These experiments that probe macroscopic, low energy, and seemingly classical aspects, have the potential to reveal underlying microscopic, high energy, unification scale quantum connections between gravity and electromagnetism.
SPEED OF GRAVITY AND GRAVITOMAGNETISM
Authors: PASCUAL-SÁNCHEZ J.-F.
Published: February 2005

A vJ/c correction to the Shapiro time delay seems verified by a 2002 Jovian observation by VLBI. In this Essay, this correction is interpreted as an effect of the aberration of light in an optically refractive medium which supplies an analog of Jupiter's gravity field rather than as a measurement of the speed of gravity, as it was first proposed by other authors. The variation of the index of refraction is induced by the Lorentz invariance of the weak gravitational field equations for Jupiter in a uniform translational slow motion with velocity vJ=13.5 km / s . The correction on time delay and deflection is due not to the Kerr (or Lense-Thirring) stationary gravitomagnetic field of Jupiter, but to its Schwarzschild gravitostatic field when measured from the barycenter of the solar system.
MIRROR MATTER-TYPE DARK MATTER
Authors: FOOT R.
Published: February 2005

There are six main things which any non-baryonic dark matter theory should endeavour to explain: (1) The basic dark matter particle properties [mass, stability, darkness]; (2) The similarity in cosmic abundance between ordinary and non-baryonic dark matter, ΩB~Ω dark ; (3) Large scale structure formation; (4) Microlensing (MACHO) events; (5) Asymptotically flat rotation curves in spiral galaxies; (6) The impressive DAMA/NaI annual modulation signal. Only mirror matter-type dark matter appears capable of explaining all six of these desirable features. The purpose of this article is to provide an up-to-date and pedagogical review of this dark matter candidate.
TORSION GRAVITY: A REAPPRAISAL
Authors: ARCOS H. I. , PEREIRA J. G.
Published: February 2005

The role played by torsion in gravitation is critically reviewed. After a description of the problems and controversies involving the physics of torsion, a comprehensive presentation of the teleparallel equivalent of general relativity is made. According to this theory, curvature and torsion are alternative ways of describing the gravitational field, and consequently related to the same degrees of freedom of gravity. However, more general gravity theories, like for example Einstein–Cartan and gauge theories for the Poincaré and the affine groups, consider curvature and torsion as representing independent degrees of freedom. By using an active version of the strong equivalence principle, a possible solution to this conceptual question is reviewed. This solution ultimately favors the teleparallel point of view, and consequently the completeness of general relativity. A discussion of the consequences for gravitation is presented.
PROBING GRAVITATIONAL INTERACTIONS OF ELEMENTARY PARTICLES
Authors: FENG JONATHAN L. , RAJARAMAN ARVIND , TAKAYAMA FUMIHIRO
Published: February 2005

The gravitational interactions of elementary particles are suppressed by the Planck scale M*~1018 GeV and are typically expected to be far too weak to be probed by experiments. We show that, contrary to conventional wisdom, such interactions may be studied by particle physics experiments in the next few years. As an example, we consider conventional supergravity with a stable gravitino as the lightest supersymmetric particle. The next-lightest supersymmetric particle (NLSP) decays to the gravitino through gravitational interactions after about a year. This lifetime can be measured by stopping NLSPs at colliders and observing their decays. Such studies will yield a measurement of Newton's gravitational constant on unprecedentedly small scales, shed light on dark matter, and provide a window on the early universe.
PULSAR KICKS FROM NEUTRINO OSCILLATIONS
Authors: KUSENKO ALEXANDER
Published: February 2005

Neutrino oscillations in a core-collapse supernova may be responsible for the observed rapid motions of pulsars. Given the present bounds on the neutrino masses, the pulsar kicks require a sterile neutrino with mass 2–20 keV and a small mixing with the active neutrinos. The same particle can be the cosmological dark matter. Its existence can be confirmed the by the X-ray telescopes if they detect a 1–10 keV photon line from the decays of the relic sterile neutrinos. In addition, one may be able to detect gravity waves from a pulsar being accelerated by neutrinos in the event of a nearby supernova.
A SECRET TUNNEL THROUGH THE HORIZON
Authors: PARIKH MAULIK
Published: February 2005

Hawking radiation is often intuitively visualized as particles that have tunneled across the horizon. Yet, at first sight, it is not apparent where the barrier is. Here I show that the barrier depends on the tunneling particle itself. The key is to implement energy conservation, so that the black hole contracts during the process of radiation. A direct consequence is that the radiation spectrum cannot be strictly thermal. The correction to the thermal spectrum is of precisely the form that one would expect from an underlying unitary quantum theory. This may have profound implications for the black hole information puzzle.
THE QUANTUM GRAVITATIONAL BLACK HOLE IS NEITHER BLACK NOR WHITE
Authors: SINGH T. P. , VAZ CENALO
Published: February 2005

Understanding the end state of black hole evaporation, the microscopic origin of black hole entropy, the information loss paradox, and the nature of the singularity arising in gravitational collapse — these are outstanding challenges for any candidate quantum theory of gravity. Recently, a midisuperspace model of quantum gravitational collapse has been solved using a lattice regularization scheme. It is shown that the mass of an eternal black hole follows the Bekenstein spectrum, and a related argument provides a fairly accurate estimate of the entropy. The solution also describes a quantized mass–energy distribution around a central black hole, which in the WKB approximation, is precisely Hawking radiation. The leading quantum gravitational correction makes the spectrum non-thermal, thus providing a plausible resolution of the information loss problem.
EXPERIMENTAL DESIGN FOR THE LATOR MISSION
Authors: TURYSHEV SLAVA G. , SHAO MICHAEL , NORDTVEDT KENNETH L.
Published: February 2005

This paper discusses experimental design for the Laser Astrometric Test Of Relativity (LATOR) mission. LATOR is designed to reach unprecedented accuracy of 1 part in 108 in measuring the curvature of the solar gravitational field as given by the value of the key Eddington post-Newtonian parameter γ. This mission will demonstrate the accuracy needed to measure effects of the next post-Newtonian order (∝G2) of light deflection resulting from gravity's intrinsic non-linearity. LATOR will provide the first precise measurement of the solar quadrupole moment parameter, J2, and will improve determination of a variety of relativistic effects including Lense–Thirring precession. The mission will benefit from the recent progress in the optical communication technologies — the immediate and natural step above the standard radio-metric techniques. The key element of LATOR is a geometric redundancy provided by the laser ranging and long-baseline optical interferometry. We discuss the mission and optical designs, as well as the expected performance of this proposed mission. LATOR will lead to very robust advances in the tests of fundamental physics: this mission could discover a violation or extension of general relativity, or reveal the presence of an additional long range interaction in the physical law. There are no analogs to the LATOR experiment; it is unique and is a natural culmination of solar system gravity experiments.
FROM NUCLEAR PHYSICS TO PHYSICS BEYOND THE STANDARD MODEL: FIRST EVIDENCE FOR LEPTON NUMBER VIOLATION AND THE MAJORANA CHARACTER OF NEUTRINOS
Authors: KLAPDOR-KLEINGROTHAUS H. V.
Published: February 2005

Nuclear double beta decay provides an extraordinarily broad potential to search for beyond-standard-model physics. The occurrence of the neutrinoless decay(0νββ) mode has fundamental consequences: first, the total lepton number is not conserved, and second, the neutrino is a Majorana particle. Furthermore, the measured effective mass provides an absolute scale of the neutrino mass spectrum. In addition, double beta experiments yield sharp restrictions for other beyond-standard-model physics. These include SUSY models (R-parity breaking and conserving), leptoquarks (leptoquark-Higgs coupling), compositeness, left-right symmetric models (right-handed W boson mass), test of special relativity and of the equivalence principle in the neutrino sector and others. First evidence for neutrinoless double beta decay was reported by the HEIDELBERG–MOSCOW experiment in 2001. The HEIDELBERG–MOSCOW experiment is by far the most sensitive0νββ experiment since more than 10 years. It is operating 11 kg of enriched76Ge in the GRAN SASSO Underground Laboratory. The analysis of the data taken from 2 August 1990–20 May 2003 is presented here. The collected statistics is 71.7 kg y. The background achieved in the energy region of the Q value for double beta decay is 0.11 events/kg y keV. The two-neutrino accompanied half-life is determined on the basis of more than 100,000 events to be [Formula: see text] years. The confidence level for the neutrinoless signal has been improved to a 4.2σ level. The half-life is [Formula: see text] years. The effective neutrino mass deduced is (0.2–0.6) eV (99.73% C.L.), with the consequence that neutrinos have degenerate masses. The sharp boundaries for other beyond SM physics, mentioned above, are comfortably competitive to the corresponding results from high-energy accelerators like TEVATRON, HERA, etc.
CHARGE CONJUGATION AND LENSE–THIRRING EFFECT: A NEW ASYMMETRY
Authors: AHLUWALIA-KHALILOVA D. V.
Published: February 2005

This essay presents a new asymmetry that arises from the interplay of charge conjugation and Lense–Thirring effect. When applied to Majorana neutrinos, the effects predicts [Formula: see text] oscillations in gravitational environments with rotating sources. Parameters associated with astrophysical environments indicate that the presented effect is presently unobservable for solar neutrinos. But, it will play an important role in supernova explosions, and carries relevance for the observed matter–antimatter asymmetry in the universe.
PRIVATE AND SOCIAL INCENTIVES TOWARDS INVESTMENT IN PRODUCT DIFFERENTIATION
Authors: CELLINI ROBERTO , LAMBERTINI LUCA
Published: February 2005

We consider a dynamic oligopoly where firms invest to increase product differentiation and an externality effect operates in the R&D activity. We compare the steady state solutions under alternative decision rules, namely, the open-loop and the closed-loop Nash equilibrium. Significant differences emerge, concerning the effect of the number of firms upon the optimal degree of product differentiation. We also compare the private optima with the social optimum, and derive implications concerning the social desirability of different decision rules.
A NOTE ON CLOSEDNESS UNDER MOULIN REDUCTION
Authors: HWANG YAN-AN
Published: February 2005

We will find 3 maximal subclasses with respect to essential, superadditive and convex games, respectively such that a game is in one subclass, so are its reduced games.
COMPACTNESS AND EXISTENCE RESULTS FOR DEGENERATE CRITICAL ELLIPTIC EQUATIONS
Authors: FELLI VERONICA , SCHNEIDER MATTHIAS
Published: February 2005

This paper is devoted to the study of degenerate critical elliptic equations of Caffarelli–Kohn–Nirenberg type. By means of blow-up analysis techniques, we prove an a priori estimate in a weighted space of continuous functions. From this compactness result, the existence of a solution to our problem is proved by exploiting the homotopy invariance of the Leray–Schauder degree.
ON HEISENBERG INEQUALITY
Authors: STAN AUREL
Published: February 2005

A Heisenberg inequality, involving a differentiation operator, its adjoint, and the second quantization operator of a unitary operator, is proved in the context of white noise analysis.
ON EXTENSIONS OF HARDY'S INEQUALITIES
Authors: GALAKTIONOV VICTOR A.
Published: February 2005

We study possible extensions of Hardy's inequalities induced by second, fourth and sixth-order linear differential operators with singular potentials.
THE HOPF CONJECTURE FOR MANIFOLDS WITH ABELIAN GROUP ACTIONS
Authors: RONG XIAOCHUN , SU XIAOLE
Published: February 2005

Let M be a closed even n-manifold of positive sectional curvature on which a torus Tk acts isometrically. We show that if [Formula: see text] (respectively, k > 1) for n ≠ 12 (respectively, n = 12), then the Euler characteristic of each Tk-fixed point component is positive. This implies that the Euler characteristic of M is positive. We also extend this result to an isometric elementary p-group [Formula: see text]-action on a closed manifold of positive sectional curvature.
THE SMOOTHNESS OF RIEMANNIAN SUBMERSIONS WITH NON-NEGATIVE SECTIONAL CURVATURE
Authors: CAO JIANGUO , SHAW MEI-CHI
Published: February 2005

Let Mn be a complete, non-compact and C∞-smooth Riemannian manifold with non-negative sectional curvature. Suppose that [Formula: see text] is a soul of Mn given by the fundamental theory of Cheeger and Gromoll, and suppose that [Formula: see text] is a distance non-increasing retraction from the whole manifold to the soul (e.g. the retraction given by Sharafutdinov). Then we show that the retraction Ψ above must give rise to a C∞-smooth Riemannian submersion from Mn to the soul [Formula: see text]. Moreover, we derive a new flat strip theorem associated with the Cheeger–Gromoll convex exhaustion for the manifold above.
Black Middle-Class Neighborhoods
Authors: Pattillo Mary
Published: February 2005

The black middle class received little scholarly attention from the 1960s through the 1980s, when the emphasis was on studying the black urban poor. Recently, however, there has been an increase in attention to this group and their residential environs. This review covers the topics of racial and class segregation, the comparative well-being of black middle-class neighborhoods, and residential preferences, with some attention to black suburbanization and black gentrification. Research findings clearly show that middle-class blacks in the United States have more favorable residential outcomes than poor blacks but still live in poorer neighborhoods than the majority of whites on all measures. Ethnographic studies explore this marginal position in more depth. I argue that if racial integration is the remedy to various racial disparities, then the more fruitful endeavor may be to study the ideologies, practices, and cultures of white neighborhoods, rather than black ones.
Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1 gene expression in brown adipose tissue
Authors: Koban Michael , Swinson Kevin L.
Published: February 2005

A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing ∼11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT.
Quantification of K+ secretion through apical low-conductance K channels in the CCD
Authors: Gray Daniel A. , Frindt Gustavo , Palmer Lawrence G.
Published: February 2005

Outward and inward currents through single small-conductance K+ (SK) channels were measured in cell-attached patches of the apical membrane of principal cells of the rat cortical collecting duct (CCD). Currents showed mild inward rectification with high [K+] in the pipette (Kp+), which decreased as Kp+ was lowered. Inward conductances had a hyperbolic dependence on Kp+ with half-maximal conductance at ∼20 mM. Outward conductances, measured near the reversal potential, also increased with Kp+ from 15 pS (Kp+ = 0) to 50 pS (Kp+ = 134 mM). SK channel density was measured as the number of conducting channels per patch in cell-attached patches. As reported previously, channel density increased when animals were on a high-K diet for 7 days. Addition of 8-cpt-cAMP to the bath at least 5 min before making a seal increased SK channel density to an even greater extent, although this increase was not additive with the effect of a high-K diet. In contrast, increases in Na channel activity, assessed as the whole cell amiloride-sensitive current, due to K loading and 8-cpt-cAMP treatment were additive. Single-channel conductances and channel densities were used as inputs to a simple mathematical model of the CCD to predict rates of transepithelial Na+ and K+ transport as a function of apical Na+ permeability and K+ conductance, basolateral pump rates and K+ conductance, and the paracellular conductance. With measured values for these parameters, the model predicted transport rates that were in good agreement with values measured in isolated, perfused tubules. The number and properties of SK channels account for K+ transport by the CCD under all physiological conditions tested.
Efficacy and Safety of 0.1% Retinaldehyde/ 6% Glycolic Acid (Diacnéal®) for Mild to Moderate Acne vulgaris
Authors: Poli F. , Ribet V. , Lauze C. , Adhoute H. , Morinet P.
Published: February 2005

Background: Retinaldehyde and glycolic acid are both efficient in acne. Objective: To evaluate the efficacy and tolerability of a 0.1% retinaldehyde/6% glycolic acid combination (Diacnéal®) for mild to moderate acne vulgaris. Methods: Overall physician and patient ratings of acne symptom severity and tolerance were performed at baseline, months 1, 2 and 3. Results: Mean numbers of papules, pustules and comedones were significantly reduced from month 1 onwards. A significant advantage of Diacnéal over vehicle was demonstrated on the percentages of patients with ongoing healing lesions at month 2, healing ancient lesions from month 1 and patients with ‘important/very important’ global improvement from month 2 (50.0 vs. 26.3%) confirmed by patients at month 3 (86.1 vs. 58.8%). Products were well tolerated; only 1 patient had to stop the treatment. Conclusions: Diacnéal, a combination of 0.1% retinaldehyde/6% glycolic acid, is effective and well tolerated in mild to moderate acne vulgaris.
The Depigmenting Effect of RALGA in C57BL/6 Mice
Authors: Kasraee B. , Tran C. , Sorg O. , Saurat J.-H.
Published: February 2005

Background: It has been known for a long time that the topical use of retinoic acid (RA) produces mild depigmentation of human skin. However, RA has two major disadvantages for its utilisation as a topical depigmenting compound. First, RA can act as an irritant and can produce considerable erythema and exfoliation of skin. Second, RA has a relatively weak depigmenting ability compared to other known depigmenting chemicals. Objective: In this study, we show that RALGA, a combination of the less irritant retinoid retinaldehyde (RAL; 0.1%) and glycolic acid (6.4%), has a higher skin-depigmenting potential than RA 0.05% in the tail skin of C57BL/6 mice. This effect was observed in reducing the number of functioning melanocytes and/or in inhibiting their ability to synthesise melanin. In addition, the visually recognisable depigmenting effect of RALGA was evident earlier than that of RA, i.e. only after 1 week of application. RALGA may therefore serve as a depigmenting product for the treatment of skin hyperpigmentary disorders. Postacne hyperpigmented lesions represent a very common pigmentary problem among acne patients. RALGA may thus act as an anti-acne product, due to the presence of RAL – an RA precursor – which could simultaneously remove the postacne hyperpigmented lesions in such patients.
Topical Retinaldehyde with Glycolic Acid: Study of Tolerance and Acceptability in Association with Anti-Acne Treatments in 1,709 Patients
Authors: Dréno B. , Nocera T. , Verrière F. , Vienne M.P. , Ségard C. , Vitse S. , Carré C.
Published: February 2005

Background: Retinaldehyde (RAL), a key metabolite between vitamin A and retinoic acid, acts by modulating differentiation and proliferation of keratinocytes, which is of interest in acne lesions, mainly retentional lesions. Glycolic acid increases the exfoliation of corneocytes explaining its mild activity on retentional lesions. Thus, RAL and glycolic acid combined in the same product (Diacnéal®) have complementary activities which can be of interest for acne patients. The aim of this study was to evaluate the tolerance of Diacnéal used by 1,709 acne patients in combination with their usual acne products except retinoids. Results: This study demonstrated a very good tolerance of Diacnéal when used with other acne treatments for 90 days. Complaints about side-effects were rare. Moreover, the significant decrease in both inflammatory and retentional lesions between day 0 and day 90 indicates that Diacnéal could amplify the efficiency of other anti-acne products used at the same time by the patients. The subjective evaluation of the preparation’s efficacy by investigators and patients was strongly favourable. Conclusion: These data show that a combination of RAL 0.1% and glycolic acid 6% may be used in association with other topical anti-acne treatments (benzoyl peroxide and topical antibiotics) with an excellent tolerance.
RALGA (Diacnéal®), a Retinaldehyde and Glycolic Acid Association and Postinflammatory Hyperpigmentation in Acne – A Review
Authors: Katsambas A.D.
Published: February 2005

Acne vulgaris affects 3 out of 4 adolescents and usually vanishes at the end of puberty with either no sequelae or mild to moderate sequelae, such as postinflammatory hyperpigmenation (PIH), which may result in psychological and emotional damages. The poor tolerability of the actual treatments (secondary inflammation) is a hindrance to therapy. Retinaldehyde (RAL), a precursor of retinoic acid, has shown depigmenting activity. Glycolic acid (GA) decreases the excess of pigment by a wounding and re-epithelization process. Thus, a synergistic effect was expected from the combination of RAL 0.1% and GA 6% RALGA (Diacnéal®) in the treatment of acne vulgaris and PIH. Efficacy results of preclinical and clinical trials tend to confirm the expectations for both acne and PIH treatment. A good tolerability was observed. In conclusion, the cosmetic cream Diacnéal is a well-tolerated treatment for the prevention and healing of PIH in acne patients.
Mixing Glycolic Acid with Retinaldehyde: RALGA, a Technical Achievement
Authors: Bordat P. , Chesnoy S.
Published: February 2005

Background: The use of retinaldehyde or glycolic acid was found to be effective in topical acne treatments. Objective: The aim of this study was thus to take advantage of the possible synergistic effect between retinaldehyde and glycolic acid and to combine the latter in a single formulation, in other words, in an oil-in-water emulsion. Methods: A certain number of critical parameters were taken into account when designing the formulation, i.e. solubility of retinaldehyde and glycolic acid, pH of the finished product and insufficient stability of retinaldehyde notably in the presence of water. Consequently, the oil components, which form the oily phase of the emulsion, were carefully selected according to the solubility of retinaldehyde. Moreover, we aimed at obtaining adequate emulsion stability so that a large amount of water could be used to make the hydroxy acid soluble. Results and Conclusion: The best retinaldehyde-glycolic acid (RALGA) formulation developed had a low pH (around 3.5) and, when stored at 40°C, revealed a good stability. Finally, the antibacterial activity of this formulation was also tested in vitro against Propionibacterium acnes and showed antibacterial results after only 5 min of contact.
Sucrose Fermentation by Saccharomyces cerevisiae Lacking Hexose Transport
Authors: Batista Anderson S. , Miletti Luiz C. , Stambuk Boris U.
Published: February 2005

Sucrose is the major carbon source used by Saccharomyces cerevisiae during production of baker’s yeast, fuel ethanol and several distilled beverages. It is generally accepted that sucrose fermentation proceeds through extracellular hydrolysis of the sugar, mediated by the periplasmic invertase, producing glucose and fructose that are transported into the cells and metabolized. In the present work we analyzed the contribution to sucrose fermentation of a poorly characterized pathway of sucrose utilization by S. cerevisiae cells, the active transport of the sugar through the plasma membrane and its intracellular hydrolysis. A yeast strain that lacks the major hexose transporters (hxt1–hxt7 and gal2) is incapable of growing on or fermenting glucose or fructose. Our results show that this hxt-null strain is still able to ferment sucrose due to direct uptake of the sugar into the cells. Deletion of the AGT1 gene, which encodes a high-affinity sucrose-H+ symporter, rendered cells incapable of sucrose fermentation. Since sucrose is not an inducer of the permease, expression of the AGT1 must be constitutive in order to allow growth of the hxt-null strain on sucrose. The molecular characterization of active sucrose transport and fermentation by S. cerevisiae cells opens new opportunities to optimize yeasts for sugarcane-based industrial processes.
The Gellan Gum Biosynthetic Genes gelC and gelE Encode Two Separate Polypeptides Homologous to the Activator and the Kinase Domains of Tyrosine Autokinases
Authors: Moreira Leonilde M. , Hoffmann Karen , Albano Helena , Becker Anke , Niehaus Karsten , Sá-Correia Isabel
Published: February 2005

The high-molecular-weight exopolysaccharide gellan is an important commercial gelling agent produced in high yield by the Gram-negative bacterium Sphingomonas elodea ATCC 31461. The cluster of genes required for gellan biosynthesis contains the genes gelC and gelE. These encode for two polypeptides homologous to the activator domain and the kinase domain, respectively, of bacterial autophosphorylating tyrosine kinases involved in polysaccharide chain length determination. The GelC/GelE pair is an exception to the biochemically characterized Gram-negative tyrosine autokinases since it consists of two polypeptides instead of a single one. The deletion of gelC or gelE resulted in the abolishment of gellan in the culture medium confirming their role in gellan biosynthesis. In addition, ATP-binding assays confirmed the predicted ATP-binding ability of GelE. Interestingly, GelE contains an unusual Walker A sequence (ASTGVGCS), where the invariant lysine is replaced by a cysteine. This residue was replaced by alanine or lysine and although both mutant proteins were able to restore gellan production by complementation of the gelE deletion mutant to the production level observed with native GelE, only the mutated GelE where the cysteine was replaced by alanine was demonstrated to bind ATP in vitro. The importance of specific tyrosine residues present in the C-terminal domain of GelE in gellan assembly was also determined. The tyrosine residue at position 198 appears to be essential for the synthesis of high-molecular-weight gellan, although other tyrosine residues may additionally contribute to GelE biological function.
Pharmacology of RALGA, a Mixture of Retinaldehyde and Glycolic Acid
Authors: Tran Christian , Kasraee Behrooz , Grand Denise , Carraux Pierre , Didierjean Liliane , Sorg Olivier , Saurat Jean-Hilaire
Published: February 2005

Background: Retinoids and α-hydroxy acids (AHAs) are major compounds in topical therapy. They exert distinct but potentially complementary activities. However, their association is limited by their respective irritating potential. Recently, the first association between a retinoid and an AHA has been achieved; this formulation (RALGA) associates retinaldehyde (RAL) – a precursor of retinoic acid (RA) – and glycolic acid (GA) – an AHA. Objective: To study the pharmacological properties of RALGA. Methods: The bioavailability of RAL into the skin after topical RALGA was studied by HPLC, and its bioconversion to RA was analysed by measuring the enzyme activity of retinaldehyde dehydrogenase and the RA content in the epidermis and dermis. The retinoid activity of RALGA was studied on the modulation of Hhb4 keratin mRNA on the tail of C57BL/6 mice, and its comedolytic properties on the size and density of dermal cysts and the morphology of sebaceous glands in hairless mice. Results: Epidermal and dermal concentrations of RAL and RA were higher after RALGA treatment, as compared to both RAL 0.1% alone and RA 0.05% alone; this indicates that the presence of GA favours the bioavailability and biotransformation of RAL into RA. The retinoid activity of RALGA (suppression of Hhb4 mRNA keratin) was similar to that of RAL alone, indicating that the presence of GA does not interfere with specific retinoid activity; GA alone had no effect in this test, which confirms the specificity of Hhb4 mRNA keratin modulation for retinoid activity. The diameter and the density of dermal cysts as well as the size of sebaceous glands were significantly decreased by RALGA. Conclusion: These observations indicate that the addition of an AHA such as GA to a retinoid such as RAL results in a better bioavailability of the retinoid, thus a higher delivery of RA, which potentiates the biological activities of the retinoid. This combination allows a delivery of high amounts of RA in the skin while preventing the side-effects usually observed with high concentrations of topical RA.
HIV Dermatology in Switzerland – From the Beginning to the Present
Authors: Itin Peter H. , Fistarol Susanna K.
Published: February 2005

The panendemic of HIV has markedly influenced the dermatology of our generation. This new infection produced atypical manifestations of known dermatological diseases. And beyond that, mucocutaneous diseases emerged, which had not yet been described. Classical epidemiological studies concluded that clustering of AIDS cases could be explained only if AIDS was an infection transmitted by sexual activity or blood. Switzerland was hit early on by the HIV epidemic, and Theo Rufli, the leading expert on sexually transmitted diseases in our country, was involved from the beginning. He contributed with his team to a better delineation of the cutaneous manifestations of HIV infection by directing one of the largest prospective studies on the natural course of cutaneous manifestations of HIV. In addition, he participated in studies which documented new skin diseases in HIV-infected patients. From the very beginning of the epidemic in Switzerland, Theo Rufli founded an organization which helped patients cope with their diagnosis. In Basel, an anonymous consultation facility was established. Theo Rufli also strongly supported the ‘Stop AIDS’ campaign. This review looks back on the history of HIV in Switzerland and especially in Basel.
Preimplantation Genetic Diagnosis:
Authors: Shahine Lora K. , Caughey Aaron B.
Published: February 2005

Preimplantation genetic diagnosis (PGD) can provide genetic information on embryos obtained through in vitro fertilization (IVF), allowing implantation of embryos identified as unaffected with a given genetic or chromosomal disorder. With the availability of increasingly sophisticated genetic testing, its use has advanced from the selection of female embryos for the prevention of X-linked genetic diseases to testing for single gene disorders via PCR. Recently, PGD has also been used in the setting of assisted reproductive technology to select for chromosomally normal embryos in an effort to increase the rates of implantation and successful pregnancy. As the number of patients undergoing IVF increases, the indications for its use broadens, and more mutations underlying genetic disorders are identified, PGD is becoming more widespread. As this evolution continues, recognition of the limitations of PGD, as well as ethical concerns regarding use and misuse of this technology, need to be considered by patients, clinicians, and policy makers.
Error Analysis of MRI and Leksell Stereotactic Frame Target Localization in Deep Brain Stimulation Surgery
Authors: Simon Scott L. , Douglas Pamela , Baltuch Gordon H. , Jaggi Jurg L.
Published: February 2005

Stereotactic deep brain stimulation (DBS) is the surgical treatment of choice for medication-refractory patients with Parkinson’s disease and essential tremor. The subthalamic nucleus and ventral intermediate nucleus of the thalamus appear to be effective targets for electrode placement. Because these targets are small and encased in fiber tracts, their localization can be exceedingly difficult. However, the precision of electrode placement is crucial for obtaining successful results. Currently, surgeons rely on preoperative MRI or CT images to derive stereotactic coordinates for targeting sites such as the subthalamic nucleus and ventral intermediate nucleus of the thalamus coupled with microelectrode recordings during surgery for proper electrode placement. However, it has been argued that the stereotactic head frame produces detrimental artifacts during MRI. We examined MRI images taken from 11 patients undergoing repeat DBS surgery, and determined the coordinates of the previously placed electrode. We then set the Leksell G stereotactic frame to these coordinates and obtained fluoroscope-localizing images. Using MATLAB image analysis tools, we were able to quantify the 3-dimensional error in target localization by measuring the distance from the electrode tip to the targeted coordinate. The mean errors were 0.09 ± 0.34 mm perpendicular, lateral to medial, 0.01 ± 0.32 perpendicular, posterior to anterior, and –0.08 ± 0.33 mm parallel to the electrode, superior to inferior. According to statistical analysis, the error was random and did not seem to move in any predictable fashion. Therefore, we conclude that preoperative MRI images can be safely used in DBS surgery, and they do not negatively affect its accuracy.
Enhanced Antiplatelet Effects of Clopidogrel plus Acetylsalicylic Acid Compared with Acetylsalicylic Acid Alone or Combined with Extended-Release Dipyridamole in Healthy Volunteers
Authors: Caplain H.
Published: February 2005

Background: Previous studies have shown the potential benefit of using antiplatelet agents with complementary modes of action. Methods: Using a crossover design, the ex vivo antiplatelet effects of 10 days’ treatment with clopidogrel 75 mg + acetylsalicylic acid (ASA) 75 mg daily, ASA 75 mg/day, or extended-release dipyridamole 200 mg/low-dose ASA 25 mg twice daily were compared, using various platelet agonists. Results: Clopidogrel + ASA was significantly more effective than dipyridamole + ASA in inhibiting collagen-induced platelet aggregation in whole blood (mean 44.9 ± 5.6% inhibition vs. 16.5 ± 6.7%; p = 0.0009). Clopidogrel + ASA was significantly more effective than ASA or dipyridamole + ASA in inhibiting ADP-induced platelet aggregation in whole blood (p≤ 0.0001) and platelet-rich plasma (PRP) (p≤ 0.0001), and in inhibiting collagen-induced aggregation in PRP (p ≤ 0.0001). ASA alone and clopidogrel + ASA were significantly more effective than dipyridamole + ASA in inhibiting arachidonic acid-induced platelet aggregation in whole blood (p ≤ 0.0001). Conclusions: Based on ex vivo platelet aggregometry, clopidogrel + ASA is a more potent antiplatelet regimen than either ASA alone or the marketed combination of dipyridamole + ASA. However, the clinical significance of this finding remains to be confirmed.
A Case-Control Analysis of Intra-Arterial Urokinase Thrombolysis in Acute Cardioembolic Stroke
Authors: Inoue Takeshi , Kimura Kazumi , Minematsu Kazuo , Yamaguchi Takenori
Published: February 2005

Background: Intra-arterial urokinase (IA-UK) thrombolysis is frequently given in Japan to selected patients with acute cerebral artery occlusion. However, it is not clear whether or not IA-UK thrombolysis has an efficacy for acute stroke patients. The purpose of this study was to assess the effects of IA-UK thrombolysis in acute cardioembolic stroke patients, by performing a case-control analysis using data from Japan’s Multicenter Stroke Investigator’s Collaboration (J-MUSIC). Methods: 16,922 acute ischemic stroke patients were enrolled into J-MUSIC. From these patients, we selected 91 patients (UK group) who met the following criteria: treatment with IA-UK; 20–75 years of age; cardioembolic stroke; presenting with a carotid stroke; admission within 4.5 h of symptom onset, and a National Institutes of Health Stroke Scale (NIHSS) score of 5–22 points on admission. A control group of 182 patients without IA-UK treatment and matched to the NIHSS score, gender, and age was chosen. We compared the modified Rankin scale (mRS) score at discharge and the mortality between the 2 groups. Results: In both groups, the mean age was 65 ± 8 years, and the median NIHSS score was 14. The mean interval between symptom onset and UK administration was 3.4 ± 1.3 h, and the IA-UK dose was 392,000 ± 200,000 units. The mRS score at discharge was lower in the UK group than in the control group (mean, SD, median; 2.8, 2.9, 2 in UK group vs. 3.3, 1.8, 4, in the control, respectively p = 0.031). A favorable outcome (mRS of 0–2) was more frequently observed in the UK group (50.5%) than in the control group (34.1%, p = 0.0124). No difference in the mortality rate was seen between the UK group (11.0%) and the control group (13.3%). As well, there was no difference in the length of hospital stay between the UK group (46 ± 41 days, mean ± SD) and the control group (42 ± 42 days, mean ± SD). Conclusions: IA-UK thrombolytic therapy may improve the outcome in hyperacute cardioembolic stroke patients.
Reduced Frequency of Embolic Signals in Severe Carotid Stenosis with Poststenotic Flow Velocity Reduction
Authors: Goertler Michael , Blaser Till , Guhr Susanne , Lotze Heike , Heisinger Jane , Kropf Siegfried , Wallesch Claus-Werner
Published: February 2005

Background: We aimed to investigate the effect of poststenotic low blood flow in patients with recently symptomatic severe carotid stenosis on arterio-arterial embolism. Methods: Analyses based on a series of 206 consecutive patients (155 men and 51 women, mean age 65.3 years) with a nondisabling ischemic event in the anterior circulation ≤30 days (median 4.5) before presentation and diagnosis of ipsilateral carotid artery stenosis/occlusion (≧30% local diameter reduction). All patients underwent Doppler/duplex sonography, which included measurement of poststenotic flow velocity as an indicator for poststenotic blood flow as well as a 1-hour transcranial Doppler monitoring for the detection of embolic signals. Results: Thirty-seven of two hundred and six patients had very severe stenosis which was associated with reduced poststenotic flow velocity (<20 cm/s systolic) in 17 patients. Probability of embolic signals increased with increasing degree of stenosis and was maximal in patients with stenoses ≧90% local diameter reduction if poststenotic flow velocity was not reduced. Reduced poststenotic flow velocity in patients with very severe stenosis was associated with a significantly lower frequency of embolic signals compared to patients with the same degree of stenosis but no velocity reduction (adjusted odds ratio 0.15, 95% confidence interval 0.025–0.897, p = 0.038, adjustment for antiplatelet medication and time since ischemia). Conclusions: Low poststenotic flow velocity behind very severe internal carotid stenosis reduces the otherwise high frequency of embolic signals in recently symptomatic patients corroborating the hypothesis that reduced blood flow across carotid stenosis causes reduced embolism.
Immunoglobulin Replacement Therapy in Primary Antibody Deficiency Diseases – Maximizing Success
Authors: Durandy Anne , Wahn Volker , Petteway Steve , Gelfand Erwin W.
Published: February 2005

Antibody or humoral immunodeficiencies comprise the largest group of primary immunodeficiency diseases. Since the first description of patients with low gammaglobulin levels more than four decades ago, a great wealth of information has been accumulated. Especially in the last several years, the application of molecular and genetic techniques has unraveled many of these disorders, identifying disorders of B cell development, failure of class switch recombination and abnormalities of specific antibody production. Regardless of the underlying defect, the mainstay of therapy has been and remains immunoglobulin (Ig) replacement therapy, currently by intravenous infusion or subcutaneous injection. With advances in manufacturing, a number of products are not only safe for intravenous administration but doses can be increased to provide even more effective infection prophylaxis. However, manufacturing processes, methods of viral inactivation and removal and final composition differ widely among the available preparations. How these variables impact clinical outcome is not clear, but they have the potential to do so. As a result, careful selection of an intravenous immunoglobulin (IVIG), matching patient needs and risks to those risks associated with a specific IVIG, is necessary to optimize outcomes and maximize the success of Ig replacement therapy.