The dynamical nature of time

It is usually assumed that the "$t$" parameter in the equations of dynamics can be identified with the indication of the pointer of a clock. Things are not so easy, however. In fact, since the equations of motion can be written in terms of $t$ but also of $t'=f(t)$, $f$ being any well behaved function, each one of those infinite parametric times $t'$ is as good as the Newtonian one to study classical dynamics. Here we show that the relation between the mathematical parametric time $t$ in the equations of dynamics and the physical dynamical time $\sigma$ that is measured with clocks is more complex and subtle than usually assumed. These two times, therefore, must be carefully distinguished since their difference may have significant consequences. Furthermore, we show that not all the dynamical clock-times are necessarily equivalent and that the observational fingerprint of this non-equivalence has the same form as that of the Pioneer anomaly.Comment: 13 pages, no figure

What is Missing for the Full Deployment of Mobile Search Services? Results from a Survey with Experts

Web search providers have developed a highly successful business model, which has rendered them amongst some of the most profitable companies operating on the internet. Many observers regard mobile search as the next new big market. In contrast to search on PCs, however, the provision of search on mobiles is still in its infancy. In order to shed light on the real prospects of mobile search we performed a two-round Delphi exercise with experts, in which we included two innovative elements. First, the Delphi exercise included seven forward-looking scenarios for discussion. Then, the second round of the Delphi was carried out during a workshop with 19 of the original 61 participants involved. In this paper we present the findings from the discussions of this final round. Our study confirms the high expectations put into the mobile search market. We found that this optimism is rooted in the view that critical technological components are already available. Our paper argues that the technology push is not yet matched by a corresponding market pull. Web search engines, mobile phone manufacturers, and telecom operators are already starting to take action to place themselves in a favourable position. They are exploring trial applications, but business models are still unclear and companies are experimenting with very different approaches. Our Delphi study identifies interfaces as critical for increased mobile search usage. Moreover, experts think that perceived usefulness is valuable but trust is essential and that privacy should be seen as an opportunity rather than a constraint. The paper concludes with some suggestions for fostering innovation, growth and competitiveness in the mobile search domain by increasing the interoperability of services, assuring the openness and mash-ups of content and services, and developing personal identity data management systems to improve user acceptance and enhance trust

Factors required for mobile search going mainstream

This article aims to review the technological and socio-economic conditions which will influence the development of the mobile search market

1/N_c and 1/n preasymptotic corrections to Current-Current correlators

We obtain the corrections in $1/n$ and in $1/\ln n$ ($n$ is the principal quantum number of the bound state) of the decay constants of scalar and pseudoscalar currents in two and four dimensions in the large $N_c$. We obtain them from the operator product expansion provided a model for the large $n$ mass spectrum is given. In the two-dimensional case the spectrum is known and the corrections obtained in this paper are model independent. We confirm these results by confronting them with the numerical solution of the 't Hooft model. We also consider a model at finite $N_c$ and obtain the associated decay constants that are consistent with perturbation theory. This example shows that that the inclusion of perturbative corrections, or finite $N_c$ effects, to the OPE does not constrain the slope of the Regge trajectories, which remain a free parameter for each different channel.Comment: 29 pages, 11 figures. Two references adde

Electronic decoupling of polyacenes from the underlying metal substrate by sp ³ carbon atoms

We report on the effect of sp3 hybridized carbon atoms in acene derivatives adsorbed on metal surfaces, namely decoupling the molecules from the supporting substrates. In particular, we have used a Ag(100) substrate and hydrogenated heptacene molecules, in which the longest conjugated segment determining its frontier molecular orbitals amounts to five consecutive rings. The non-planarity that the sp3 atoms impose on the carbon backbone results in electronically decoupled molecules, as demonstrated by the presence of charging resonances in dI/dV tunneling spectra and the associated double tunneling barriers, or in the Kondo peak that is due to a net spin S=1/2 of the molecule as its LUMO becomes singly charged. The spatially dependent appearance of the charging resonances as peaks or dips in the differential conductance spectra is further understood in terms of the tunneling barrier variation upon molecular charging, as well as of the different orbitals involved in the tunneling process

Leading Chiral Logarithms to the Hyperfine Splitting of the Hydrogen and Muonic Hydrogen

We study the hydrogen and muonic hydrogen within an effective field theory framework. We perform the matching between heavy baryon effective theory coupled to photons and leptons and the relevant effective field theory at atomic scales. This matching can be performed in a perturbative expansion in alpha, 1/m_p and the chiral counting. We then compute the O(m_{l_i}^3 alpha^5/m_p^2 x logarithms) contribution (including the leading chiral logarithms) to the Hyperfine splitting and compare with experiment. They can explain about 2/3 of the difference between experiment and the pure QED prediction when setting the renormalization scale at the rho mass. We give an estimate of the matching coefficient of the spin-dependent proton-lepton operator in heavy baryon effective theory.Comment: 17 pages, LaTeX, minor changes, one reference adde

Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates

BACKGROUND: Adeno-associated vectors (rAAV) have been used to attain long-term liver gene expression. In humans, the cellular immune response poses a serious obstacle for transgene persistence while neutralizing humoral immunity curtails re-administration. Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria) benefits from liver gene transfer in mouse models and clinical trials are about to begin. In this study, we sought to study in non-human primates the feasibility of repeated gene-transfer with intravenous administration of rAAV5 vectors under the effects of an intensive immunosuppressive regimen and to analyze its ability to circumvent T-cell immunity and thereby prolong transgene expression. METHODS: Three female Macaca fascicularis were intravenously injected with 1x1013 genome copies/kg of rAAV5 encoding the human PBGD. Mycophenolate mofetil (MMF), anti-thymocyte immunoglobulin, methylprednisolone, tacrolimus and rituximab were given in combination during 12 weeks to block T- and B-cell mediated adaptive immune responses in two macaques. Immunodeficient and immunocompetent mice were intravenously injected with 5x1012 genome copies/kg of rAAV5-encoding luciferase protein. Forty days later MMF, tacrolimus and rituximab were daily administrated to ascertain whether the immunosuppressants or their metabolites could interfere with transgene expression. RESULTS: Macaques given a rAAV5 vector encoding human PBGD developed cellular and humoral immunity against viral capsids but not towards the transgene. Anti-AAV humoral responses were attenuated during 12 weeks but intensely rebounded following cessation of the immunosuppressants. Accordingly, subsequent gene transfer with a rAAV5 vector encoding green fluorescent protein was impossible. One macaque showed enhanced PBGD expression 25 weeks after rAAV5-pbgd administration but overexpression had not been detected while the animal was under immunosuppression. As a potential explanation, MMF decreases transgene expression in mouse livers that had been successfully transduced by a rAAV5 several weeks before MMF onset. Such a silencing effect was independent of AAV complementary strand synthesis and requires an adaptive immune system. CONCLUSIONS: These results indicate that our transient and intensive pharmacological immunosuppression fails to improve AAV5-based liver gene transfer in non-human primates. The reasons include an incomplete restraint of humoral immune responses to viral capsids that interfere with repeated gene transfer in addition to an intriguing MMF-dependent drug-mediated interference with liver transgene expression

Contemporary percutaneous treatment of unprotected left main coronary stenoses: initial results from a multicenter registry analysis 1994-1996.

BACKGROUND: Coronary artery bypass surgery (CABG) has been considered the therapy of choice for patients with unprotected left main (ULMT) coronary stenoses. Selected single-center reports suggest that the results of percutaneous intervention may now approach those of CABG. METHODS AND RESULTS: To assess the results of percutaneous ULMT treatment from a wide variety of experienced interventional centers, we requested data on consecutive patients treated after January 1, 1994, from 25 centers. One hundred seven patients were identified who were treated either electively (n=91) or for acute myocardial infarction (n=16). Of patients treated electively, 25% were considered inoperable, and 27% were considered high risk for bypass surgery. Primary treatment included stents (50%), directional atherectomy (24%), and balloon angioplasty (20%). Follow-up was 98.8% complete at 15+/-8 months. Results varied considerably, depending on presentation and treatment. For patient

Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events : The ODYSSEY OUTCOMES Trial

The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths. This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES. Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated, linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death. With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk. In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS