bluuebunny/crossref_metadata_2025 huggingface dataset:
Central auditory processing of noncontextual consonance in music: An evoked potential study
Authors: Itoh Kosuke , Suwazono Shugo , Nakada Tsutomu
Published: January 2011

The consonance of individual chords presented out of musical context, or the noncontextual consonance of chords, is usually defined as the absence of roughness, which is a sensation perceived when slightly mistuned frequencies are not clearly resolved in the cochlea. The present work uses evoked potentials to demonstrate that the absence of roughness is not sufficient to explain the entirety of noncontextual consonance perception. Presented with a random sequence of various pure-tone intervals (0–13 semitones), listeners’ cerebral cortical activities distinguished these stimuli according to their noncontextual consonance in a manner consistent with standard musical practice, even when the intervals exceeded the critical bandwidth (approximately three semitones). The roughness-based model of noncontextual consonance could not account for this result because these wide intervals had indistinguishably low levels of roughness. Further, this effect was evident only in musicians, indicating plasticity in the underlying neural mechanisms. The results are consistent with the hypothesis that, although the absence of roughness may represent an important aspect of noncontextual consonance, properties of intervals other than those related to roughness also contribute to this perception, underpinned by neural activity in the central auditory system that can be plastically modified by experience.
Theoretical and experimental analysis of the electromechanical behavior of a compact spherical loudspeaker array for directivity control
Authors: Pasqual Alexander Mattioli , Herzog Philippe , Arruda José Roberto de França
Published: January 2011

Sound directivity control is made possible by a compact array of independent loudspeakers operating at the same frequency range. The drivers are usually distributed over a sphere-like frame according to a Platonic solid geometry to obtain a highly symmetrical configuration. The radiation pattern of spherical loudspeaker arrays has been predicted from the surface velocity pattern by approximating the drivers membranes as rigid vibrating spherical caps, although a rigorous assessment of this model has not been provided so far. Many aspects concerning compact array electromechanics remain unclear, such as the effects on the acoustical performance of the drivers interaction inside the array cavity, or the fact that voltages rather than velocities are controlled in practice. This work presents a detailed investigation of the electromechanical behavior of spherical loudspeaker arrays. Simulation results are shown to agree with laser vibrometer measurements and experimental sound power data obtained for a 12-driver spherical array prototype at low frequencies, whereas the non-rigid body motion and the first cavity eigenfrequency yield a discrepancy between theoretical and experimental results at high frequencies. Finally, although the internal acoustic coupling affects the drivers vibration in the low-frequency range, it does not play an important role on the radiated sound power.
Temporal properties of perceptual calibration to local and broad spectral characteristics of a listening context
Authors: Alexander Joshua M. , Kluender Keith R.
Published: January 2011

The auditory system calibrates to reliable properties of a listening environment in ways that enhance sensitivity to less predictable (more informative) aspects of sounds. These reliable properties may be spectrally local (e.g., peaks) or global (e.g., gross tilt), but the time course over which the auditory system registers and calibrates to these properties is unknown. Understanding temporal properties of this perceptual calibration is essential for revealing underlying mechanisms that serve to increase sensitivity to changing and informative properties of sounds. Relative influence of the second formant (F2) and spectral tilt was measured for identification of /u/ and /i/ following precursor contexts that were harmonic complexes with frequency-modulated resonances. Precursors filtered to match F2 or tilt of following vowels induced perceptual calibration (diminished influence) to F2 and tilt, respectively. Calibration to F2 was greatest for shorter duration precursors (250 ms), which implicates physiologic and/or perceptual mechanisms that are sensitive to onsets. In contrast, calibration to tilt was greatest for precursors with longer durations and higher repetition rates because greater opportunities to sample the spectrum result in more stable estimates of long-term global spectral properties. Possible mechanisms that promote sensitivity to change are discussed.
Regular patterns stabilize auditory streams
Authors: Bendixen Alexandra , Denham Susan L. , Gyimesi Kinga , Winkler István
Published: January 2011

The auditory system continuously parses the acoustic environment into auditory objects, usually representing separate sound sources. Sound sources typically show characteristic emission patterns. These regular temporal sound patterns are possible cues for distinguishing sound sources. The present study was designed to test whether regular patterns are used as cues for source distinction and to specify the role that detecting these regularities may play in the process of auditory stream segregation. Participants were presented with tone sequences, and they were asked to continuously indicate whether they perceived the tones in terms of a single coherent sequence of sounds (integrated) or as two concurrent sound streams (segregated). Unknown to the participant, in some stimulus conditions, regular patterns were present in one or both putative streams. In all stimulus conditions, participants’ perception switched back and forth between the two sound organizations. Importantly, regular patterns occurring in either one or both streams prolonged the mean duration of two-stream percepts, whereas the duration of one-stream percepts was unaffected. These results suggest that temporal regularities are utilized in auditory scene analysis. It appears that the role of this cue lies in stabilizing streams once they have been formed on the basis of simpler acoustic cues.
Dynamic behavior of the circular membrane of an electrostatic microphone: Effect of holes in the backing electrode
Authors: Lavergne Thomas , Durand Stéphane , Bruneau Michel , Joly Nicolas , Rodrigues Dominique
Published: January 2011

Today, several applications require using electrostatic microphones in environments and/or in frequency ranges, which are significantly different from those they were designed for. When low uncertainties on the behavior of acoustic fields, generated or measured by these transducers, are required, the displacement field of the diaphragm of the transducers (which can be highly nonuniform in the highest frequency range) must be characterized with an appropriate accuracy. An analytical approach, which leads to results depending on the location of the holes in the backing electrode (i.e., depending on the azimuthal coordinate) not available until now (regarding the displacement field of the membrane in the highest frequency range, up to 100 kHz), is presented here. The holes and the slit surrounding the electrode are considered as localized sources described by their volume velocity in the propagation equation governing the pressure field in the air gap (not by nonuniform boundary conditions on the surface of the backing electrode as usual). Experimental results, obtained from measurements of the displacement field of the membrane using a laser scanning vibrometer, are presented and compared to the theoretical results.
On the third- and fourth-order constants of incompressible isotropic elasticity
Authors: Destrade Michel , Ogden Raymond W.
Published: January 2011

Consider the constitutive law for an isotropic elastic solid with the strain-energy function expanded up to the fourth order in the strain and the stress up to the third order in the strain. The stress–strain relation can then be inverted to give the strain in terms of the stress with a view to considering the incompressible limit. For this purpose, use of the logarithmic strain tensor is of particular value. It enables the limiting values of all nine fourth-order elastic constants in the incompressible limit to be evaluated precisely and rigorously. In particular, it is explained why the three constants of fourth-order incompressible elasticity μ, A¯, and D¯ are of the same order of magnitude. Several examples of application of the results follow, including determination of the acoustoelastic coefficients in incompressible solids and the limiting values of the coefficients of nonlinearity for elastic wave propagation.
A binaural beat constructed from a noise (L)
Authors: Akeroyd Michael A.
Published: January 2011

The binaural beat has been used for over 100 years as a stimulus for generating the percept of motion. Classically the beat consists of a pure tone at one ear (e.g., 500 Hz) and the same pure tone at the other ear but shifted upward or downward in frequency (e.g., 501 Hz). An experiment and binaural computational analysis are reported which demonstrate that a more powerful motion percept can be obtained by applying the concept of the frequency shift to a noise, via an upward or downward shift in the frequency of the Fourier components of its spectrum.
Recovery of distortion-product otoacoustic emissions after a 2-kHz monaural sound-exposure in humans: Effects on fine structures
Authors: Aranda de Toro Miguel Angel , Ordoñez Rodrigo , Reuter Karen , Hammersh⊘i Dorte
Published: January 2011

A better understanding of the vulnerability of the fine structures of distortion-product otoacoustic emissions (DPOAEs) after acoustic overexposure may improve the knowledge about DPOAE generation, cochlear damage, and lead to more efficient diagnostic tools. It is studied whether the DPOAE fine structures of 16 normal-hearing human subjects are systematically affected after a moderate monaural sound-exposure of 10 min to a 2-kHz tone normalized to an exposure level LEX,8h of 80 dBA. DPOAEs were measured before and in the following 70 min after the exposure. The experimental protocol allowed measurements with high time and frequency resolution in a 1/3-octave band centered at 3 kHz. On average, DPOAE levels were reduced approximately 5 dB in the entire measured frequency-range. Statistically significant differences in pre- and post-exposure DPOAE levels were observed up to 70 min after the end of the sound exposure. The results show that the effects on fine structures are highly individual and no systematic change was observed.
Low Mach number analysis of idealized thermoacoustic engines with numerical solution
Authors: Hireche Omar , Weisman Catherine , Baltean-Carlès Diana , Quéré Patrick Le , Bauwens Luc
Published: January 2011

A model of an idealized thermoacoustic engine is formulated, coupling nonlinear flow and heat exchange in the heat exchangers and stack with a simple linear acoustic model of the resonator and load. Correct coupling results in an asymptotically consistent global model, in the small Mach number approximation. A well-resolved numerical solution is obtained for two-dimensional heat exchangers and stack. The model assumes that the heat exchangers and stack are shorter than the overall length by a factor of the order of a representative Mach number. The model is well-suited for simulation of the entire startup process, whereby as a result of some excitation, an initially specified temperature profile in the stack evolves toward a near-steady profile, eventually reaching stationary operation. A validation analysis is presented, together with results showing the early amplitude growth and approach of a stationary regime. Two types of initial excitation are used: Random noise and a small periodic wave. The set of assumptions made leads to a heat-exchanger section that acts as a source of volume but is transparent to pressure and to a local heat-exchanger model characterized by a dynamically incompressible flow to which a locally spatially uniform acoustic pressure fluctuation is superimposed.
Mechanisms underlying the detection of frequency modulation
Authors: Ernst Stephan M. A. , Moore Brian C. J.
Published: January 2011

Frequency modulation detection limens (FMDLs) were measured for carrier frequencies (fc) of 1000, 4000, and 6000 Hz, using modulation frequencies (fm) of 2 and 10 Hz and levels of 20 and 60 dB sensation level (SL), both with and without random amplitude modulation (AM), applied in all intervals of a forced-choice trial. The AM was intended to disrupt excitation-pattern cues. At 60 dB SL, the deleterious effect of the AM was smaller for fm = 2 than for fm = 10 Hz for fc = 1000 and 4000 Hz, respectively, while for fc = 6000 Hz the deleterious effect was large and similar for the two values of fm. This is consistent with the idea that, for fc below about 5000 Hz and fm = 2 Hz, frequency modulation can be detected via changes in phase locking over time. However, at 20 dB SL, the deleterious effect of the added AM for fc = 1000 and 4000 Hz was similar for the two values of fm, while for fc = 6000 Hz, the deleterious effect of the AM was greater for fm = 10 than for fm = 2 Hz. It is suggested that, at low SLs, the auditory filters become relatively sharp and phase locking weakens, so that excitation-pattern cues influence FMDLs even for low fc and low fm.
The use of frequency resolution in echolocation for modeling three dimensional environments
Authors: Huebschman Benjamin D.
Published: January 2011

Bats use echolocation to navigate three dimensional obstacles while locating, identifying, and engaging targets. A theory is offered of image processing during the search and navigation phase of echolocation that uses Doppler frequency shifts. The information in frequency changes across the angle of elevation can be used to generate a three dimensional model of the environment when combined with the timing and the relative amplitude of the returned signals. The mathematics of frequency shifts for an emitter traveling at a large fraction of the velocity of propagation (c) is presented. Reported behavior that can be explained by this phenomenon is discussed.
Mutational Analyses of Open Reading Frames within the
vraSR
Operon and Their Roles in the Cell Wall Stress Response of
Staphylococcus aureus
Authors: McCallum N. , Meier P. Stutzmann , Heusser R. , Berger-Bächi B.
Published: January 2011

The exposure of
Staphylococcus aureus
to a broad range of cell wall-damaging agents triggers the induction of a cell wall stress stimulon (CWSS) controlled by the VraSR two-component system. The
vraSR
genes form part of the four-cistron autoregulatory operon
orf1-yvqF-vraS-vraR
. The markerless inactivation of each of the genes within this operon revealed that
orf1
played no observable role in CWSS induction and had no influence on resistance phenotypes for any of the cell envelope stress-inducing agents tested. The remaining three genes were all essential for the induction of the CWSS, and mutants showed various degrees of increased susceptibility to cell wall-active antibiotics. Therefore, the role of YvqF in
S. aureus
appears to be opposite that in other Gram-positive bacteria, where YvqF homologs have all been shown to inhibit signal transduction. This role, as an activator rather than repressor of signal transduction, corresponds well with resistance phenotypes of ΔYvqF mutants, which were similar to those of ΔVraR mutants in which CWSS induction also was completely abolished. Resistance profiles of ΔVraS mutants differed phenotypically from those of ΔYvqF and ΔVraR mutants on many non-ß-lactam antibiotics. ΔVraS mutants still became more susceptible than wild-type strains at low antibiotic concentrations, but they retained larger subpopulations that were able to grow on higher antibiotic concentrations than ΔYvqF and ΔVraR mutants. Subpopulations of ΔVraS mutants could grow on even higher glycopeptide concentrations than wild-type strains. The expression of a highly sensitive CWSS-luciferase reporter gene fusion was up to 2.6-fold higher in a ΔVraS than a ΔVraR mutant, which could be linked to differences in their respective antibiotic resistance phenotypes. Bacterial two-hybrid analysis indicated that the integral membrane protein YvqF interacted directly with VraS but not VraR, suggesting that it plays an essential role in sensing the as-yet unknown trigger of CWSS induction.
Artemether and Artesunate Show the Highest Efficacies in Rescuing Mice with Late-Stage Cerebral Malaria and Rapidly Decrease Leukocyte Accumulation in the Brain
Authors: Clemmer L. , Martins Y. C. , Zanini G. M. , Frangos J. A. , Carvalho L. J. M.
Published: January 2011

The murine model of cerebral malaria (ECM) caused by
Plasmodium berghei
ANKA (PbA) infection in susceptible mice has been extensively used for studies of pathogenesis and identification of potential targets for human CM therapeutics. However, the model has been seldom explored to evaluate adjunctive therapies for this malaria complication. A first step toward this goal is to define a treatment protocol with an effective antimalarial drug able to rescue mice presenting late-stage ECM. We evaluated the efficacy of artemisinin, artemether, artesunate, and quinine given intraperitoneally once a day, and combinations with mefloquine, in suppressing PbA infection in mice with moderate parasitemia. Artemether, artesunate, and quinine were then evaluated for efficacy in rescuing PbA-infected mice with ECM, strictly defined by using objective criteria based on the presentation of clinical signs of neurological involvement, degree of hypothermia, and performance in a set of six motor behavior tests. Artemether at 25 mg/kg presented the fastest parasite killing ability in 24 h and fully avoided recrudescence in a 5-day treatment protocol. Artemether and artesunate were equally effective in rescuing mice with late-stage ECM (46 and 43% survival, respectively), whereas quinine had a poor performance (12.5% survival). Artemether caused a marked decrease in brain leukocyte accumulation 24 h after the first dose. In conclusion, artemether and artesunate are effective in rescuing mice with late-stage ECM and decrease brain inflammation. In addition, the described protocols for more strict clinical evaluation and for rescue treatment provide a framework for studies of CM adjunctive therapies using this mouse model.
In Vitro
Activities of New 2-Substituted Quinolines against
Leishmania donovani
Authors: Loiseau Philippe M. , Gupta Suman , Verma Aditya , Srivastava Saumya , Puri S. K. , Sliman Faten , Normand-Bayle Marie , Desmaele Didier
Published: January 2011

A series of 9 quinolines and 18 styrylquinolines was evaluated for the drugs'
in vitro
antileishmanial activities and cytotoxicities. The 7-aroylstyrylquinoline scaffold appeared to be the most promising one, with the most interesting compound, no. 35, exhibiting a 50% inhibitory concentration (IC
50
) of 1.2 μM and a selectivity index value of 121.5. Compound 35 was 10-fold and 8-fold more active than miltefosine and sitamaquine, the reference compounds, with selectivity indexes 607-fold and 60-fold higher, respectively.
Identification of the Minimal Active Sequence of an Anti-Influenza Virus Peptide
Authors: Jones Jeremy C. , Settles Erik W. , Brandt Curtis R. , Schultz-Cherry Stacey
Published: January 2011

The antiviral peptide, entry blocker (EB), inhibits influenza virus replication by preventing attachment to cells. Here, we identified the minimal and optimal EB sequence that retained antiviral activity with a 50% inhibitory concentration (IC50) and 50% effective concentration (EC50) similar to those of the full-length EB peptide and several truncated variants that possessed up to 10-fold lower IC50s. These data have implications for improving the antiviral efficacy of EB-derived peptides while decreasing production costs and easing synthesis.
Interleukin-4-Inducing Principle from
Schistosoma mansoni
Eggs Contains a Functional C-Terminal Nuclear Localization Signal Necessary for Nuclear Translocation in Mammalian Cells but Not for Its Uptake
Authors: Kaur Ishwinder , Schramm Gabriele , Everts Bart , Scholzen Thomas , Kindle Karin B. , Beetz Christian , Montiel-Duarte Cristina , Blindow Silke , Jones Arwyn T. , Haas Helmut , Stolnik Snjezana , Heery David M. , Falcone Franco H.
Published: January 2011

Interleukin-4-inducing principle from schistosome eggs (IPSE/alpha-1) is a protein produced exclusively by the eggs of the trematode
Schistosoma mansoni
. IPSE/alpha-1 is a secretory glycoprotein which activates human basophils via an IgE-dependent but non-antigen-specific mechanism. Sequence analyses revealed a potential nuclear localization signal (NLS) at the C terminus of IPSE/alpha-1. Here we show that this sequence (125-PKRRRTY-131) is both necessary and sufficient for nuclear localization of IPSE or IPSE-enhanced green fluorescent protein (EGFP) fusions. While transiently expressed EGFP-IPSE/alpha-1 was exclusively nuclear in the Huh7 and U-2 OS cell lines, a mutant lacking amino acids 125 to 134 showed both nuclear and cytoplasmic staining. Moreover, insertion of the IPSE/alpha-1 NLS into a tetra-EGFP construct rendered the protein nuclear. Alanine scanning mutagenesis revealed a requirement for the KRRR residues. Fluorescence microscopy depicted, and Western blotting further confirmed, that recombinant IPSE/alpha-1 protein added exogenously is rapidly internalized by CHO cells and accumulates in nuclei in an NLS-dependent manner. A mutant protein in which the NLS motif was disrupted by triple mutation (RRR to AAA) was able to penetrate CHO cells but did not translocate to the nucleus. Furthermore, the uptake of native glycosylated IPSE/alpha-1 was confirmed in human primary monocyte-derived dendritic cells and was found to be a calcium- and temperature-dependent process. Live-cell imaging showed that IPSE/alpha-1 is not targeted to lysosomes. In contrast, peripheral blood basophils do not take up IPSE/alpha-1 and do not require the presence of an intact NLS for activation. Taken together, our results suggest that IPSE/alpha-1 may have additional nuclear functions in host cells.
Evaluation of the toxicity of Adonis aestivalis in sheep
Authors: Woods L. W. , Puschner B. , Filigenzi M. S. , Woods D. M. , George L. W.
Published: January 2011

To determine the toxicity of Adonis aestivalis (adonis) in sheep, adult Suffolk ewes were administered 1 per cent bodyweight adonis via surgically placed rumen cannulas in an acute, high‐dose toxicity study, and 0.2 per cent bodyweight daily in a two‐week, low‐dose toxicity study. The ewes received cardiac examinations before dosing, 24 and 48 hours after dosing with 1 per cent bodyweight adonis, and after continuous low‐dose administration. All the ewes administered adonis had transient sinus arrhythmias after receiving 1 per cent bodyweight adonis. Two of the three ewes had transient reduced fractional shortening after administration with 1 per cent bodyweight adonis; the same two ewes had reduced fractional shortening after the low‐dose treatment regimen. No gross or microscopic lesions were seen when the ewes were examined postmortem at the end of the study.
THE CONNECTION BETWEEN "EMERGENCE OF TIME FROM QUANTUM GRAVITY" AND "DYNAMICAL COLLAPSE OF THE WAVE FUNCTION IN QUANTUM MECHANICS"
Authors: SINGH TEJINDER P.
Published: January 2011

There are various reasons to believe that quantum theory could be an emergent phenomenon. Trace dynamics is an underlying classical dynamics of noncommuting matrices, from which quantum theory and classical mechanics have been shown to emerge, in the thermodynamic approximation. However, the time that is used to describe evolution in quantum theory is an external classical time, and is in turn expected to be an emergent feature — a relic of an underlying theory of quantum gravity. In this essay we borrow ideas from trace dynamics to show that classical time is a thermodynamic approximation to an operator time in quantum gravitational physics. This prediction will be put to test by ongoing laboratory experiments attempting to construct superposed states of macroscopic objects.
SCALAR AVERAGING IN COSMOLOGY
Authors: COLEY A. A.
Published: January 2011

The averaging problem in cosmology is of considerable importance for the correct interpretation of cosmological data. In this essay an approach to averaging based on scalar curvature invariants is presented, which gives rise to significant effects on cosmological evolution.
VACUUM STRUCTURE AND DARK ENERGY
Authors: LABUN LANCE , RAFELSKI JOHANN
Published: January 2011

We consider that the universe is trapped in an excited vacuum state and the resulting excitation energy provides the observed dark energy. We explore the conditions under which this situation can arise from physics already known. Considering the example of how macroscopic quantum electrodynamic fields alter the vacuum structure, we find that the energy scale 1 meV–1 eV is particularly interesting. We discuss how dark energy of this form is accessible to laboratory experiments.
HOLLOWGRAPHY DRIVEN HOLOGRAPHY: BLACK HOLE WITH VANISHING VOLUME INTERIOR
Authors: DAVIDSON AHARON , GURWICH ILYA
Published: January 2011

Hawking–Bekenstein entropy formula seems to tell us that no quantum degrees of freedom can reside in the interior of a black hole. We suggest that this is a consequence of the fact that the volume of any interior sphere of finite surface area simply vanishes. Obviously, this is not the case in general relativity. However, we show that such a phenomenon does occur in various gravitational theories which admit a spontaneously induced general relativity. In such theories, due to a phase transition (one-parameter family degenerates) which takes place precisely at the would-have-been horizon, the recovered exterior Schwarzschild solution connects, by means of a self-similar transition profile, with a novel "hollow" interior exhibiting a vanishing spatial volume and a locally varying Newton constant. This constitutes the so-called "hollowgraphy" driven holography.
PHOTON MASS AND VERY LONG BASELINE INTERFEROMETRY
Authors: ACCIOLY ANTONIO , HELAYËL-NETO JOSÉ , SCATENA ESLLEY
Published: January 2011

A relation between the photon mass, its frequency, ν, and the deflection parameter, γ, determined by experimentalists (that characterizes the contribution of space curvature to gravitational deflection) is found. This amazing result allows us to conclude that the knowledge of the parameters ν and γ is all we need to set up gravitational bounds on the photon mass. By considering as inputs the most recent measurements of the solar gravitational deflection of radio waves obtained via the Very Long Baseline Interferometry, upper bounds on the photon mass are estimated.
TESTING HAWKING PARTICLE CREATION BY BLACK HOLES THROUGH CORRELATION MEASUREMENTS
Authors: BALBINOT R. , CARUSOTTO I. , FABBRI A. , RECATI A.
Published: January 2011

Hawking's prediction of thermal radiation by black holes has been shown by Unruh to be expected also in condensed matter systems. We show here that in a black hole-like configuration realized in a BEC this particle-creation does indeed take place and can be unambiguously identified via a characteristic pattern in the density–density correlations. This opens the concrete possibility of the experimental verification of this effect.
FROM BLACK HOLES TO EMERGENT GRAVITY
Authors: BANERJEE RABIN
Published: January 2011

Many inequivalent approaches to study black holes yield identical results. Any meaningful theory of gravity should explain the origin of this property. Here we show that the basic holomorphic modes characterizing the underlying two-dimensional conformal symmetry near the horizon bring about this universality. Moreover these modes lead to a law of equipartition of energy for black holes which suggests a statistical origin of gravity. This emergent nature of gravity is further bolstered by showing the equivalence of entropy with the action (S = -(i/ℏ), I) and expressing the generalized Smarr formula for mass as a thermodynamic relation, S = E/2T where S, E and T are the entropy, energy and temperature, respectively, of a black hole.
SPACE–TIME ENERGY–MOMENTUM, THE OBSERVER AND UNCERTAINTY IN GENERAL RELATIVITY
Authors: COOPERSTOCK F. I. , DUPRE M. J.
Published: January 2011

In this essay, we introduce a new approach to energy–momentum in general relativity. Space–time, as opposed to space, is recognized as the necessary arena for its examination, leading us to define new extended space–time energy and momentum constructs. From local and global considerations, we conclude that the Ricci tensor is the required element for a localized expression of energy–momentum to include the gravitational field. We present and rationalize a fully invariant extended expression for space–time energy, guided by Tolman's well-known energy integral for an arbitrary bounded stationary system. This raises fundamental issues which we discuss. The role of the observer emerges naturally and we are led to an extension of the uncertainty principle to general relativity, of particular relevance to ultra-strong gravity.
THE WARPING OF EXTRA SPACES ACCELERATES THE EXPANSION OF THE UNIVERSE
Authors: NEUPANE ISHWAREE P.
Published: January 2011

Generic cosmological models derived from higher-dimensional theories with warped extra-dimensions have a nonzero cosmological constant-like term induced on the 3 + 1 space–time, or a physical three-brane. In the scenario where this 3 + 1 space–time is an inflating de Sitter "bran" embedded in a higher-dimensional space–time, described by warped geometry, the four-dimensional cosmological term is determined in terms of two length scales: one is a scale associated with the size of extra-dimension(s) and the other is a scale associated with the warping of extra-space(s). The existence of this term in four dimensions provides a tantalizing possibility of explaining the observed accelerating expansion of the universe from fundamental theories of gravity, e.g. string theory.
BUILDING UP SPACE–TIME WITH QUANTUM ENTANGLEMENT
Authors: VAN RAAMSDONK MARK
Published: January 2011

In this essay, we argue that the emergence of classically connected space–times is intimately related to the quantum entanglement of degrees of freedom in a nonperturbative description of quantum gravity. Disentangling the degrees of freedom associated with two regions of space–time results in these regions pulling apart and pinching off from each other in a way that can be quantified by standard measures of entanglement.
HUGE QUANTUM GRAVITY EFFECTS IN THE SOLAR SYSTEM
Authors: PAGE DON N.
Published: January 2011

Normally one thinks of the motion of the planets around the Sun as a highly classical phenomenon, so that one can neglect quantum gravity in the solar system. However, classical chaos in the planetary motion amplifies quantum uncertainties so that they become very large, giving huge quantum gravity effects. For example, evidence suggests that Uranus may eventually be ejected from the solar system, but quantum uncertainties would make the direction at which it leaves almost entirely uncertain, and the time of its exit uncertain by about one quadrillion years. For a time a quadrillion years from now, there are huge quantum uncertainties whether Uranus will be within the solar system, within the galaxy, or even within causal contact of the galaxy.
HOW CHINESE FARMERS CHANGE CROP CHOICE TO ADAPT TO CLIMATE CHANGE
Authors: WANG JINXIA , MENDELSOHN ROBERT , DINAR ARIEL , HUANG JIKUN
Published: January 2011

A multinomial logit model is estimated across the crop choices of a sample of thousands of Chinese farmers. As temperatures warm, farmers are more likely to choose cotton and maize, but less likely to choose soybeans, and vegetables. As precipitation increases, farmers are more likely to choose wheat and less likely to choose vegetables and potatoes. We simulate how crop choice outcomes might change using the empirical results and a set of climate change predictions for 2100. The magnitude of the change is sensitive to the climate scenario and to the seasonal and regional variation of climate change predictions within China.
An Atypical Cutaneous Reaction to Rivastigmine Transdermal Patch
Authors: Grieco T. , Rossi M. , Faina V. , De Marco I. , Pigatto P. , Calvieri S.
Published: January 2011

Rivastigmine is a cholinesterase inhibitor which improves cognitive function and is currently being used in patients with mild to moderate Parkinson's and Alzheimer's dementia. This drug can be given orally or topically, as transdermal patch. The latter form is currently used for most excellent compliance and few side effects. The most common cutaneous side effects are irritative dermatitis. We report the second case of active sensitization by the rivastigmine-patch in a patient suffering from Alzheimer's dementia.
Collagen‐Based Films Containing Liposome‐Loaded Usnic Acid as Dressing for Dermal Burn Healing
Authors: Nunes Paula S. , Albuquerque-Júnior Ricardo L. C. , Cavalcante Danielle R. R. , Dantas Marx D. M. , Cardoso Juliana C. , Bezerra Marília S. , Souza Jamille C. C. , Serafini Mairim Russo , Quitans-Jr Lucindo J. , Bonjardim Leonardo R. , Araújo Adriano A. S.
Published: January 2011

The aim of this study was assess the effect of collagen‐based
films containing usnic acid as a wound dressing for dermal burn
healing. Second‐degree burn wounds were performed in forty‐five
Wistar rats, assigned into nine groups: COL—animals treated
with collagen‐based films; PHO—animals treated with collagen
films containing empty liposomes; UAL—animals treated with
collagen‐based films containing usnic acid incorporated into
liposomes. After 7, 14, and 21 days the animals were euthanized.
On 7th day there was a moderate infiltration of neutrophils, in
UAL, distributed throughout the burn wounds, whereas in COL and
PHO, the severity of the reaction was slighter and still limited
to the margins of the burn wounds. On the 14th day, the
inflammatory reaction was less intense in UAL, with remarkable
plasma cells infiltration. On the 21st day, there was reduction of
the inflammation, which was predominantly composed of plasma cells
in all groups, particularly in UAL. The use of the usnic acid
provided more rapid substitution of type‐III for type‐I collagen
on the 14th day, and improved the collagenization density on the
21st day. It was concluded that the use of reconstituted bovine
type‐I collagen‐based films containing usnic acid improved burn
healing process in rats.
Transient PI3K Inhibition Induces Apoptosis and Overcomes HGF-Mediated Resistance to EGFR-TKIs inEGFRMutant Lung Cancer
Authors: Donev Ivan S. , Wang Wei , Yamada Tadaaki , Li Qi , Takeuchi Shinji , Matsumoto Kunio , Yamori Takao , Nishioka Yasuhiko , Sone Saburo , Yano Seiji
Published: January 2011

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib, show favorable response to EGFR mutant lung cancer. However, the responders acquire resistance almost without exception. We recently reported that hepatocyte growth factor (HGF) induces EGFR-TKI resistance by activating MET that restores downstream mitogen activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K)/Akt signaling. The purpose of this study was to determine whether inhibition of PI3K, a downstream molecule of both EGFR and MET, could overcome HGF-mediated EGFR-TKI resistance in EGFR mutant lung cancer cells PC-9 and HCC827.

Experimental Design: We explored therapeutic effect of a class I PI3K inhibitor PI-103 on HGF-induced EGFR-TKI resistance in vitro and in vivo.

Results: Unlike gefitinib or erlotinib, continuous exposure with PI-103 inhibited proliferation of PC-9 and HCC827 cells, even in the presence of HGF. On the other hand, in gefitinib-resistant xenograft model by using PC-9 cells mixed with HGF high producing fibroblasts, PI-103 monotherapy did not inhibit tumor growth. However, PI-103 combined with gefitinib successfully regressed gefitinib-resistant tumor. In vitro experiments by considering short half-life of PI-103 reveal that transient exposure of PI-103 combined with gefitinib caused sustained inhibition of Akt phosphorylation, but not ERK1/2 phosphorylation, resulting in induction of tumor cell apoptosis even in the presence of HGF.

Conclusions: These results indicate that transient blockade of PI3K/Akt pathway by PI-103 and gefitinib could overcome HGF-mediated resistance to EGFR-TKIs by inducing apoptosis in EGFR mutant lung cancer. Clin Cancer Res; 17(8); 2260–9. ©2011 AACR.
Acquisition of Chemoresistance and EMT Phenotype Is Linked with Activation of the Endothelin A Receptor Pathway in Ovarian Carcinoma Cells
Authors: Rosanò Laura , Cianfrocca Roberta , Spinella Francesca , Di Castro Valeriana , Nicotra Maria Rita , Lucidi Alessandro , Ferrandina Gabriella , Natali Pier Giorgio , Bagnato Anna
Published: January 2011

Purpose: Emerging evidence suggests molecular and phenotypic association between chemoresistance and epithelial–mesenchymal transition (EMT) in cancer. Endothelin-1 (ET-1)/endothelin A receptor (ETAR) axis is implicated in the pathobiology of epithelial ovarian cancer (EOC) by driving tumor-promoting effects, including EMT. Here, we analyzed how ETAR regulates chemoresistance and EMT in EOC.

Experimental Design: The effects of ET-1 axis on cell proliferation, drug-induced apoptosis, invasiveness, and EMT were analyzed in cultured EOC cells sensitive and resistant to cisplatinum and taxol. Tumor growth in response to ETAR antagonist was examined in EOC xenografts. ETAR expression was examined in 60 human EOC tumors by immunohistochemistry and correlated with chemoresistance and EMT.

Results: In resistant EOC cells ET-1 and ETAR are upregulated, paralleled by enhanced mitogen activated protein kinase (MAPK) and Akt phosphorylation and cell proliferation. Moreover, in these cells the expression of E-cadherin transcriptional repressors, including Snail, Slug, and Twist, as well as of mesenchymal markers, such as vimentin and N-cadherin, were upregulated and linked with enhanced invasive behavior. Interestingly, ETAR blockade with zibotentan, a specific ETAR antagonist, or its silencing, downregulated Snail activity, restored drug sensitivity to cytotoxic-induced apoptosis, and inhibited the invasiveness of resistant cells. In vivo, zibotentan inhibited tumor growth of sensitive and resistant EOC xenografts, and sensitized to chemotherapy. Analysis of EOC human tissues revealed that ETAR is overexpressed in resistant tumors and is associated with EMT phenotype.

Conclusions: Our data provide the first evidence that blockade of ETAR-driven EMT can overcome chemoresistance and inhibit tumor progression, improving the outcome of EOC patients' treatment. Clin Cancer Res; 17(8); 2350–60. ©2011 AACR.
Targeted Therapy of VEGFR2 and EGFR Significantly Inhibits Growth of Anaplastic Thyroid Cancer in an Orthotopic Murine Model
Authors: Gule Maria K. , Chen Yunyun , Sano Daisuke , Frederick Mitchell J. , Zhou Ge , Zhao Mei , Milas Zvonimir L. , Galer Chad E. , Henderson Ying C. , Jasser Samar A. , Schwartz David L. , Bankson James A. , Myers Jeffrey N. , Lai Stephen Y.
Published: January 2011

Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most lethal human cancers with a median survival of 6 months. The inhibition of epidermal growth factor receptor (EGFR) alone, or with VEGF receptor 2 (VEGFR2), represents an attractive approach for treatment of ATC. Several reports have examined agents that target these receptors. However, with the misidentification of as many as 60% of all commonly used ATC cell lines, the significance of these past findings is unclear.

Experimental Design: Cell lines authenticated by short tandem repeat profiling were selected to establish xenograft tumors in an orthotopic murine model of ATC. These mice were then treated with vandetanib to evaluate its effects on ATC tumor growth. Dynamic contrast-enhanced (DCE) MRI was utilized to measure the impact of vandetanib on tumor vasculature.

Results: Vandetanib inhibited tumor growth of the ATC cell lines Hth83 and 8505C in vivo by 69.3% (P < 0.001) and 66.6% (P < 0.05), respectively, when compared with control. Significant decreases in vascular permeability (P < 0.01) and vascular volume fraction (P < 0.05) were detected by DCE-MRI in the orthotopic xenograft tumors after 1 week of treatment with vandetanib as compared with control.

Conclusion: The inhibition of EGFR and VEGFR2 by vandetanib and its tremendous in vivo antitumor activity against ATC make it an attractive candidate for further preclinical and clinical development for the treatment of this particularly virulent cancer, which remains effectively untreatable. Vandetanib disrupts angiogenesis and DCE-MRI is an effective method to quantify changes in vascular function in vivo. Clin Cancer Res; 17(8); 2281–91. ©2011 AACR.
Impact of Increased Body Mass Index on Laparoscopic Surgery for Rectal Cancer
Authors: Karahasanoglu Tayfun , Hamzaoglu Ismail , Baca Bilgi , Aytac Erman , Kirbiyik Ebru
Published: January 2011

Background: Laparoscopy was initially considered to be a risky procedure for rectal cancer patients, especially patients with an increased body weight. The literature is scarce regarding the effects of obesity on laparoscopic rectal surgery. The aim of the current study was to analyze the effect of an increased body mass index (BMI) on outcome of laparoscopic surgery for rectal cancer. Methods: Patients who underwent laparoscopic rectal resection were allocated to one of three groups according to their BMI: normal weight (BMI < 25), overweight (25 ≤ BMI < 30) and obese (BMI ≧ 30). These three groups were compared with each other in terms of patient demographics, postoperative hospital stay, postoperative complications and histopathological data. Results: There were 100 patients operated on for rectal cancer. The median BMI of the patients was 27 (range 18.5–40) kg/m2, and 43, 43 and 14 patients were classified as normal weight, overweight and obese, respectively. The conversion rate was 4.7% in the overweight group and 0% in the other groups. The proportion of complications and oncological outcomes between the groups showed no significant difference (p > 0.05). Conclusions: Apparently, increased BMI is not a contraindication for laparoscopic rectal surgery.
Chemical Production in Electrocautery Smoke by a Novel Predictive Model
Authors: Wu Y.-C. , Tang C.-S. , Huang H.-Y. , Liu C.-H. , Chen Y.-L. , Chen D.-R. , Lin Y.-W.
Published: January 2011

Objectives: The hazards of electrocautery smoke have been known for decades. However, few clinical studies have been conducted to analyze the responsible variables of the smoke production. This study collected clinical smoke samples and systematically analyzed all possible factors. Methods: Thirty diathermy smoke samples were collected during mastectomy and abdominal cavity operations. Samples were analyzed using a gas chromatographer with a flame ionization detector. Data were applied to construct prediction models for chemical production from electrosurgeries to identify all possible factors that impact chemical production during electrosurgery. Results: Toluene was detected in 27 smoke samples (90%) with concentrations of 0.003–0.463 mg/m3 and production of 176.0–2,780.0 ng. Ethyl benzene and styrene were identified in very few cases. General linear regression analysis demonstrates that surgery type, patient age, electrocautery duration and imparted coagulation energy explained 67.63% of the variation in toluene production. Conclusion: Surgery type and patient age are known prior to surgery. In terms of risk precaution, the operating team should pay close attention to exposure when certain positive factors of increasing the chemical production are known in advance.
Biocompatibility of Different Poly(Lactide-Coglycolide) Polymers Implanted into the Subconjunctival Space in Rats
Authors: Rönkkö Seppo , Kaarniranta Kai , Kalesnykas Giedrius , Uusitalo Hannu
Published: January 2011

Aims: Biomaterials are widely used in ophthalmology, and biodegradable polymers have been evaluated for use in surgery, tissue engineering and targeted drug delivery. We examined the tissue reactions attributable to 3 biodegradable polymers in the rat eye. Methods: Inion GTR™ membrane [a blend of 85:15 poly(L-lactide-coglycolide) and 70:30 poly(L-lactide-co-1,3-trimethylene carbonate) copolymers in a molar ratio of 70:30], a 50:50 molar ratio of poly(DL-lactide-coglycolide) (PDLGA 50:50), and a 85:15 molar ratio of poly(DL-lactide-coglycolide) (PDLGA 85:15) were surgically implanted into the subconjuctival space of rat eyes. Biocompatibility was evaluated by following the eyes clinically and with histo- and immunohistochemical techniques. Results: No clinical signs of inflammation were observed around the implants during follow-up. However, immunohistochemical sections revealed increased accumulation of magrophages around PDLGA 85:15 at 2 weeks and of myofibroblasts around GTR membrane material at 1 month. The order of the degradation time of the material was GTR membrane material > PDLGA 85:15 > PDLGA 50:50; Fourier transform infrared microscopy revealed some differences in the degradation behavior of the polymers. Immunohistochemical staining for plasma or cellular fibronectin was observed around all implants. Conclusions: Despite the different decay times and influences on the expression levels of fibronectins, all polymers evoked rather similar tissue reactions during the observation period. This study provides new data on the biocompatibility of biomaterials in rat eyes. Our findings of the tissue decay of the implant and biomaterial-induced tissue reaction may help in the development of better biomaterials for eye surgery with optimal drug delivery properties.
Nail Psoriasis Successfully Treated with Intralesional Methotrexate: Case Report
Authors: Sarıcaoglu Hayriye , Oz Arife , Turan Hakan
Published: January 2011

Psoriasis is a common, chronic disease which affects nearly 3% of the population. The lifetime incidence of nail involvement increases up to 80–90% for psoriatic patients. Nail psoriasis is considered a significant social problem. Many topical agents have been used for psoriatic nails with various side effects and some benefits; management is currently inconclusive. Methotrexate (MTX) is a folic acid analog, which irreversibly binds to dehydrofolate reductase and blocks deoxyribonucleic acid synthesis. It is considered a potential treatment option for rapidly growing cells and has an anti-inflammatory effect through inhibition of the polyamine pathway in autoimmune diseases. Intralesional MTX has been used successfully for various indications. We present a case successfully treated with low-dose intralesional MTX with no observed side effects in a 26-year-old female psoriatic patient suffering from nail dystrophy. In contrast, conventional topical and systemic therapies have various side effects, which limit their use. We conclude that intralesional MTX injection seems to be a safe and effective treatment option for nail psoriasis; however, large controlled studies are needed.