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We suggest that four of the deepest problems in science are closely related and may share a common resolution. These are (1) the foundational problems in quantum theory, (2) the problem of quantum gravity, (3) the role of qualia and conscious awareness in nature, (4) the nature of time. We begin by proposing an answer to the question of what a quantum event is: an event is a process in which an aspect of the world which has been indefinite becomes definite. We build from this an architecture of the world in which qualia are real and consequential and time is active, fundamental, and irreversible.

Antimicrobial resistance has grown exponentially in the last decade and become a global health threat. The antibiotic resistance crisis has guided the scientific community to explore non-conventional interventions to target resistant bacteria. Development of new technologies, such as aptamers-based treatment and diagnosis, has shown to be promising with remarkable advantages over the past five years. This narrative review aims on what is already known regarding application of aptamer technology in enterobacteria and non-fermenters, and the prospects for future achievements. A systematic search of the English literature was performed on the 7th of December 2021 to identify papers on aptamer discovery, with a focus on gram negative isolates, published from January 01, 1993, to December 07, 2021, under the topics: (aptamer OR aptamers OR SELEX) AND (bacteria OR sepsis OR non-fermenter OR Enterobacteriaceae OR infection)). The reference lists of included articles were also searched, in addition to hand-searching of various relevant high-impact journals. Out of 2,474 articles, 30 experimental studies were recruited for review, and are chronologically described. Although the number of publications regarding development of aptamers to target these pathogenic agents has increased over the years, the recent publications are mostly around diagnostic devices manufactured using previously described aptamers. There have been less than one-third of the studies describing new and specific aptamers. From the 30 selected papers, 18 are regarding non-fermenters, seven approaching multi-species of bacteria and only five regarding a single enterobacteria. Even for the newly described aptamers, most of the published papers pertain to diagnostic aptamers and only seven focus on aptamers for therapeutics. The number of aptamers with strong and specific binding capacity are still limited. Improving the current SELEX and developing more APT remains the major hurdle for aptamer related studies.

The SARS-CoV-2 Omicron variant has demonstrated increased transmissibility and ability to escape natural and vaccine-induced immunity. We aimed to characterize the duration of Omicron’s shedding by comparing viral isolation to rapid antigen test (RAT) and real-time polymerase chain reaction (RT-PCR) positivity. Thus, we performed a cross-sectional study of 30 vaccinated individuals with mild COVID-19 to evaluate the ability to infect Vero cells at day 5, 7, 10 and 14 since symptoms onset. Viral growth was observed in 46% and 20% of respiratory samples at day 5 and 7, respectively, while all were negative from day 10. RAT showed 100% of sensitivity during the first 7 days of symptoms compared to viral isolation, being a better infectivity predictor than RT-PCR Ct values. In conclusion, immunocompetent vaccinated individuals with Omicron infection can still transmit the virus on the 7th day of symptoms. This data may impact decisions on end-isolation protocols for mild COVID-19.

We describe a new form of retrocausality, which is found in the behaviour of a class of causal set theories, called energetic causal sets (ECS). These are discrete sets of events, connected by causal relations. They have three orders: (1) a birth order, which is the order in which events are generated; this is a total order which is the true causal order, (2) a dynamical partial order, which prescribes the flows of energy and momentum amongst events, (3) an emergent causal order, which is defined by the geometry of an emergent Minkowski spacetime, in which the events of the causal sets are embedded. However, the embedding of the events in the emergent Minkowski spacetime may preserve neither the true causal order in (1), nor correspond completely with the microscopic partial order in (2). We call this disordered causality, and we here demonstrate its occurrence in specific ECS models. This is the second in a series of papers centered around the question: Should we accept violations of causality as a lesser price to pay in order to keep realist formulations of quantum theory? We begin to address this in the first paper [1] and continue here by giving an explicit example of an ECS model in the classical regime, in which causality is disordered., Comment: Accepted to Physical Review D

Of all basic principles of classical physics, realism should arguably be the last to be given up when seeking a better interpretation of quantum mechanics. We examine the de Broglie-Bohm pilot wave theory as a well developed example of a realistic theory. We present three challenges to a naive reading of pilot-wave theory, each based on a system of several entangled particles. With the help of a coarse graining of pilot wave theory into a discrete system, we show how these challenges can be answered. However this comes with a cost. In the description of individual systems, particles appear to scatter off empty branches of the wave function as if they were particles, and conversely travel through particles as if they were waves. More generally, the "particles" of pilot wave theory are led by the guidance equation to move in ways no classical particle would, involving apparent violations of the principles of inertia and momentum conservation.We next argue that the aforementioned cost can be avoided within a retrocausal model. In the proposed version of the pilot wave theory, the particle is guided by a combination of advanced and retarded waves. The resulting account for quantum physics seems to have greater heuristic power, it demands less damage to intuition, and moreover provides some general hints regarding spacetime and causality. This is the first of two papers. In the second [1] we show that, in the context of an explicit model, retrocausality, with respect to an effective, emergent spacetime metric, can coexist with a strict irreversibility of causal processes., Comment: Minorly revised version. Accepted to Phys. Rev. D

We provide a new extension of general relativity (GR) which has the remarkable property of being more constrained than GR plus a cosmological constant, having one less free parameter. This is implemented by allowing the cosmological constant to have a consistent space-time variation, through coding its dynamics in the torsion tensor. We demonstrate this mechanism by adding a `quasi-topological' term to the Einstein action, which naturally realizes a dynamical torsion with an automatic satisfaction of the Bianchi identities. Moreover, variation of the action with respect to this dynamical $\Lambda$ fixes it in terms of other variables, thus providing a scenario with less freedom than general relativity with a cosmological constant. Once matter is introduced, at least in the homogeneous and isotropic reduction, $\Lambda$ is uniquely determined by the field content of the model. We make an explicit construction using the Palatini formulation of GR and describe the striking properties of this new theory. We also highlight some possible extensions to the theory. A companion paper [1] explores the Friedmann--Robertson--Walker reduction for cosmology, and future work will study Solar System tests of the theory., Comment: Companion paper to arXiv:1905.10382. Minor updates to match published version

Inserting a varying Lambda in Einstein's field equations can be made consistent with the Bianchi identities by allowing for torsion, without the need to add scalar field degrees of freedom. In the minimal such theory, Lambda is totally free and undetermined by the field equations in the absence of matter. Inclusion of matter ties Lambda algebraically to it, at least when homogeneity and isotropy are assumed, i.e. when there is no Weyl curvature. We show that Lambda is proportional to the matter density, with a proportionality constant depending on the equation of state. Unfortunately, the proportionality constant becomes infinite for pure radiation, ruling out the minimal theory prima facie despite of its novel internal consistency. It is possible to generalize the theory still without the addition of kinetic terms, leading to a new algebraically-enforced proportionality between Lambda and the matter density. Lambda and radiation may now coexist in a form consistent with Big Bang Nucleosynthesis, though this places strict constraints on the single free parameter of the theory, $\theta$. In the matter epoch Lambda behaves just like a dark matter component. Its density is proportional to the baryonic and/or dark matter, and its presence and gravitational effects would need to be included in accounting for the necessary dark matter in our Universe. This is a companion paper to Ref. [1] where the underlying gravitational theory is developed in detail., Comment: Companion paper to arXiv:1905.10380. Minor updates to match published version

In 1979 Penrose hypothesized that the arrows of time are explained by the hypothesis that the fundamental laws are time irreversible. That is, our reversible laws, such as the standard model and general relativity are effective, and emerge from an underlying fundamental theory which is time irreversible. In Cort\^{e}s and Smolin (2014a, 2014b, 2016) we put forward a research program aiming at realizing just this. The aim is to find a fundamental description of physics above the planck scale, based on irreversible laws, from which will emerge the apparently reversible dynamics we observe on intermediate scales. Here we continue that program and note that a class of discrete dynamical systems are known to exhibit this very property: they have an underlying discrete irreversible evolution, but in the long term exhibit the properties of a time reversible system, in the form of limit cycles. We connect this to our original model proposal in Cort\^{e}s and Smolin (2014a), and show that the behaviours obtained there can be explained in terms of the same phenomenon: the attraction of the system to a basin of limit cycles, where the dynamics appears to be time reversible. Further than that, we show that our original models exhibit the very same feature: the emergence of quasi-particle excitations obtained in the earlier work in the space-time description is an expression of the system's convergence to limit cycles when seen in the causal set description., Comment: 22 pages, 8 figures

Energetic causal sets are causal sets endowed by a flow of energy-momentum between causally related events. These incorporate a novel mechanism for the emergence of space-time from causal relations. Here we construct a spin foam model which is also an energetic causal set model. This model is closely related to the model introduced in parallel by Wolfgang Wieland in arXiv:1407.0025, and this construction makes use of results used there. What makes a spin foam model also an energetic causal set is Wieland's identification of new momenta, conserved at events (or four-simplices), whose norms are not mass, but the volume of tetrahedra. This realizes the torsion constraints, which are missing in previous spin foam models, and are needed to relate the connection dynamics to those of the metric, as in general relativity. This identification makes it possible to apply the new mechanism for the emergence of space-time to a spin foam model., Comment: 16 pages, 4 figures. v2 typo corrected, references added

We develop the model proposed by Cort��s, Gomes & Smolin, to predict cosmological signatures of time-asymmetric extensions of general relativity they proposed recently. Within this class of models the equation of motion of chiral fermions is modified by a torsion term. This term leads to a dispersion law for neutrinos that associates a new time-varying energy with each particle. We find a new neutrino contribution to the Friedmann equation resulting from the torsion term in the Ashtekar connection. In this note we explore the phenomenology of this term and observational consequences for cosmological evolution. We show that constraints on the critical energy density will ordinarily render this term unobservably small, a maximum of order $10^{-25}$ of the neutrino energy density today. However, if the time-asymmetric dark energy is tuned to cancel the cosmological constant, the torsion effect may be a dark matter candidate., v2 added explanations and definitions; 11 pages

We discuss degeneracies between dark energy and cosmic parameters using a fully non-perturbative and non-parametric approach. This allows us to examine the knock-on bias induced in the reconstructed dark energy equation of state, w(z), if there is a bias in the cosmic curvature or dark matter content. Assuming perfect Hubble, distance and volume measurements, we show that for z > 1, the bias in w(z) is up to two orders of magnitude larger than the corresponding errors in Ω k or Ω m .

We investigate the prior dependence on the inferred spectrum of primordial tensor perturbations, in light of recent results from BICEP2 and taking into account a possible dust contribution to polarized anisotropies. We highlight an optimized parametrization of the tensor power spectrum, and adoption of a logarithmic prior on its amplitude A(T), leading to results that transform more evenly under change of pivot scale. In the absence of foregrounds the tension between the results of BICEP2 and Planck drives the tensor spectral index n(T) to be blue tilted in a joint analysis, which would be in contradiction to the standard inflation prediction (n(T)

We describe a class of modified gravity theories that deform general relativity in a way that breaks time reversal invariance and, very mildly, locality. The algebra of constraints, local physical degrees of freedom, and their linearized equations of motion, are unchanged, yet observable effects may be present on cosmological scales, which have implications for the early history of the universe. This is achieved in the Hamiltonian framework, in a way that requires the constant mean curvature gauge conditions and is, hence, inspired by shape dynamics., 19 pages, LaTex, no figures

We provide a unified description of the hemispherical asymmetry in the cosmic microwave background generated by the mechanism proposed by Erickcek, Kamionkowski, and Carroll, using a delta N formalism that consistently accounts for the asymmetry-generating mode throughout. We derive a general form for the power spectrum which explicitly exhibits the broken translational invariance. This can be directly compared to cosmic microwave background observables, including the observed quadrupole and fNL values, automatically incorporating the Grishchuk--Zel'dovich effect. Our calculation unifies and extends previous calculations in the literature, in particular giving the full dependence of observables on the phase of our location in the super-horizon mode that generates the asymmetry. We demonstrate how the apparently different results obtained by previous authors arise as different limiting cases. We confirm the existence of non-linear contributions to the microwave background quadrupole from the super-horizon mode identified by Erickcek et al. and further explored by Kanno et al., and show that those contributions are always significant in parameter regimes capable of explaining the observed asymmetry. We indicate example parameter values capable of explaining the observed power asymmetry without violating other observational bounds., 17 pages, 2 figures, v2: changed definition of the parameter A by a factor of 2, v3: published in JCAP

We propose an approach to quantum theory based on the energetic causal sets, introduced in [1]. Fundamental processes are causal sets whose events carry momentum and energy, which are transmitted along causal links and conserved at each event. Energetic causal set models differ from other spacetime-free causal set approaches, e.g. Ref. [2] proposed causal sets based on quantum information processing systems, and Ref. [3] proposed causal sets constructed out of standard model particles. Fundamentally there are amplitudes for causal processes in energetic causal sets, but no space-time. An embedding of the causal processes in an emergent space-time arises only at the semiclassical level. Hence, fundamentally there are no commutation relations, no uncertainty principle and, indeed, no ~. All that remains of quantum theory is the relationship between the absolute value squared of complex amplitudes and probabilities. Consequently, we find that neither locality, nor non locality, are primary concepts, only causality exists at the fundamental level.

We carry out a comprehensive analysis of the simplest curvaton model, which is based on two non-interacting massive fields. Our analysis encompasses cases where the inflaton and curvaton both contribute to observable perturbations, and where the curvaton itself drives a second period of inflation. We consider both power spectrum and non-Gaussianity observables, and focus on presenting constraints in model parameter space. The fully curvaton-dominated regime is in some tension with observational data, while an admixture of inflaton-generated perturbations improves the fit. The inflating curvaton regime mimics the predictions of Nflation. Some parts of parameter space permitted by power spectrum data are excluded by non-Gaussianity constraints. The recent BICEP2 results [1] require that the inflaton perturbations provide a significant fraction of the total perturbation, ruling out the usual curvaton scenario in which the inflaton perturbations are negligible, though not the admixture regime where both inflaton and curvaton contribute to the spectrum., 7 pages, 9 figures; v2 matches journal accepted version

We argue that the observed large-scale cosmic microwave anomalies, discovered by WMAP and confirmed by the Planck satellite, are most naturally explained in the context of a marginally-open universe. Particular focus is placed on the dipole power asymmetry, via an open universe implementation of the large-scale gradient mechanism of Erickcek et al. Open inflation models, which are motivated by the string landscape and which can excite `super-curvature' perturbation modes, can explain the presence of a very-large-scale perturbation that leads to a dipole modulation of the power spectrum measured by a typical observer. We provide a specific implementation of the scenario which appears compatible with all existing constraints., 5 pages RevTeX, no figures

We describe a new class of models of quantum space-time based on energetic causal sets and show that under natural conditions space-time emerges from them. These are causal sets whose causal links are labelled by energy and momentum and conservation laws are applied at events. The models are motivated by principles we propose govern microscopic physics which posit a fundamental irreversibility of time. One consequence is that each event in the history of the universe has a distinct causal relationship to the rest; this requires a novel form of dynamics which an be applied to uniquely distinctive events. We hence introduce a new kind of deterministic dynamics for a causal set in which new events are generated from pairs of progenitor events by a rule which is based on extremizing the distinctions between causal past sets of events. This dynamics is asymmetric in time, but we find evidence from numerical simulations of a 1+1 dimensional model, that an effective dynamics emerges which restores approximate time reversal symmetry. Energetic causal set models differ from other spacetime-free causal set approaches, e.g. Ref. [1] proposed causal sets based on quantum information processing systems, and Ref. [2] proposed causal sets constructed out of standard model particles. Finally we also present a natural twistorial representation of energetic causal sets., Comment: 26 pages, 5 figures

Section 3.5 of Aihara et al. (2011) described various sources of systematic error in the astrometry of the imaging data of the Sloan Digital Sky Survey (SDSS). In addition to these sources of error, there is an additional and more serious error, which introduces a large systematic shift in the astrometry over a large area around the north celestial pole. The region has irregular boundaries but in places extends as far south as declination δ ≈ 41◦. The sense of the shift is that the positions of all sources in the affected area are offset by roughly 250 mas in a northwest direction. We have updated the SDSS online documentation to reflect these errors, and to provide detailed quality information for each SDSS field.

This report is based on the BigBOSS proposal submission to NOAO in October 2010, and reflects the project status at that time with minor updates; BigBOSS is a Stage IV ground-based dark energy experiment to study baryon acoustic oscillations (BAO) and the growth of structure with a wide-area galaxy and quasar redshift survey over 14,000 square degrees. It has been conditionally accepted by NOAO in response to a call for major new instrumentation and a high-impact science program for the 4-m Mayall telescope at Kitt Peak. The BigBOSS instrument is a robotically-actuated, fiber-fed spectrograph capable of taking 5000 simultaneous spectra over a wavelength range from 340 nm to 1060 nm, with a resolution R = 3000-4800. Using data from imaging surveys that are already underway, spectroscopic targets are selected that trace the underlying dark matter distribution. In particular, targets include luminous red galaxies (LRGs) up to z = 1.0, extending the BOSS LRG survey in both redshift and survey area. To probe the universe out to even higher redshift, BigBOSS will target bright [OII] emission line galaxies (ELGs) up to z = 1.7. In total, 20 million galaxy redshifts are obtained to measure the BAO feature, trace the matter power spectrum at smaller scales, and detect redshift space distortions. BigBOSS will provide additional constraints on early dark energy and on the curvature of the universe by measuring the Ly-alpha forest in the spectra of over 600,000 2.2 < z < 3.5 quasars. BigBOSS galaxy BAO measurements combined with an analysis of the broadband power, including the Ly-alpha forest in BigBOSS quasar spectra, achieves a FOM of 395 with Planck plus Stage III priors. This FOM is based on conservative assumptions for the analysis of broad band power (kmax = 0.15), and could grow to over 600 if current work allows us to push the analysis to higher wave numbers (kmax = 0.3). BigBOSS will also place constraints on theories of modified gravity and inflation, and will measure the sum of neutrino masses to 0.024 eV accuracy.

Using a sample of approximately 14,000 z>2.1 quasars observed in the first year of the Baryon Oscillation Spectroscopic Survey (BOSS), we measure the three-dimensional correlation function of absorption in the Lyman-alpha forest. The angle-averaged correlation function of transmitted flux (F = exp(-tau)) is securely detected out to comoving separations of 60 Mpc/h, the first detection of flux correlations across widely separated sightlines. A quadrupole distortion of the redshift-space correlation function by peculiar velocities, the signature of the gravitational instability origin of structure in the Lyman-alpha forest, is also detected at high significance. We obtain a good fit to the data assuming linear theory redshift-space distortion and linear bias of the transmitted flux, relative to the matter fluctuations of a standard LCDM cosmological model (inflationary cold dark matter with a cosmological constant). At 95% confidence, we find a linear bias parameter 0.16, Comment: many pages and figures; to be submitted to JCAP; v2: expanded section on instrument and primary reduction; minor clarifications, references; added author; matches version accepted by JCAP

Dark energy dynamics in the recent universe is influenced by its evolution through the long, matter dominated expansion history. A particular dynamical property, the flow variable, remains constant in several classes of scalar field models as long as matter dominates; the dark energy is only free to diverge in behavior at recent times. This gives natural initial conditions for Monte Carlo studies of dark energy dynamics. We propose a parametrization for the later evolution that covers a wide range of possible behaviors, is tractable in making predictions, and can be constrained by observations. We compare the approach to directly parametrizing the potential, which does not take into account the maturity of the dark energy dynamics., 12 pages, 11 figures. Accepted for publication in Phys Rev D.

We investigate the parameter space of hybrid inflation models where inflation terminates via a first-order phase transition causing nucleation of bubbles. Such models experience a tension from the need to ensure nearly scale invariant density perturbations, while avoiding a near scale-invariant bubble size distribution which would conflict observations. We perform an exact analysis of the different regimes of the models, where the energy density of the inflaton field ranges from being negligible as compared to the vacuum energy to providing most of the energy for inflation. Despite recent microwave anisotropy results favouring a spectral index less than one, we find that there are still viable models that end with bubble production and can match all available observations. As a by-product of our analysis, we also provide an up-to-date assessment of the viable parameter space of Linde's original second-order hybrid model across its full parameter range., 9 pages, 7 figures. Revised version: corrections to description of the historical development of the models. v3: Minor corrections to match version accepted by PRD

We examine the choice of scale at which constraints on inflationary observables are presented. We describe an implementation of the hierarchy of inflationary consistency equations which ensures that they remain enforced on different scales, and then seek to optimize the scale for presentation of constraints on marginalized inflationary parameters from WMAP3 data. For models with spectral index running, we find a strong variation of the constraints through the range of observational scales available, and optimize by finding the scale which decorrelates constraints on the spectral index n_S and the running. This scale is k=0.017 Mpc^{-1}, and gives a reduction by a factor of more than four in the allowed parameter area in the n_S-r plane (r being the tensor-to-scalar ratio) relative to k=0.002 Mpc^{-1}. These optimized constraints are similar to those obtained in the no-running case. We also extend the analysis to a larger compilation of data, finding essentially the same conclusions., 7 pages RevTeX4 with 9 figures included. v2: References added, new section added analyzing additional datasets alongside WMAP3. v3: Minor corrections to match version accepted by PRD

We highlight the unexpected impact of nucleosynthesis and other early universe constraints on the detectability of tracking quintessence dynamics at late times, showing that such dynamics may well be invisible until the unveiling of the Stage-IV dark energy experiments (DUNE, JDEM, LSST, SKA). Nucleosynthesis forces |w'(0)| < 0.2 for the models we consider and strongly limits potential deviations from LCDM. Surprisingly, the standard CPL parametrisation, w(z) = w_0 + w_a z/(1+z), cannot match the nucleosynthesis bound for minimally coupled tracking scalar fields. Given that such models are arguably the best-motivated alternatives to a cosmological constant these results may significantly impact future cosmological survey design and imply that dark energy may well be dynamical even if we do not detect any dynamics in the next decade., 5 pages, 2 figures. Updated to match published version

We show that the assumption of a flat universe induces critically large errors in reconstructing the dark energy equation of state at z>~0.9 even if the true cosmic curvature is very small, O(1%) or less. The spuriously reconstructed w(z) shows a range of unusual behaviour, including crossing of the phantom divide and mimicking of standard tracking quintessence models. For 1% curvature and LCDM, the error in w grows rapidly above z~0.9 reaching (50%,100%) by redshifts of (2.5,2.9) respectively, due to the long cosmological lever arm. Interestingly, the w(z) reconstructed from distance data and Hubble rate measurements have opposite trends due to the asymmetric influence of the curved geodesics. These results show that including curvature as a free parameter is imperative in any future analyses attempting to pin down the dynamics of dark energy, especially at moderate or high redshifts., 5 pages, 2 figures. To appear in JCAP

Inflationary consistency equations relate the scalar and tensor perturbations. We elucidate the infinite hierarchy of consistency equations of single-field inflation, the first of which is the well-known relation A_T^2/A_S^2 = -n_T/2 between the amplitudes and the tensor spectral index. We write a general expression for all consistency equations both to first and second-order in the slow-roll expansion. We discuss the relation to other consistency equations that have appeared in the literature, in particular demonstrating that the approximate consistency equation recently introduced by Chung and collaborators is equivalent to the second consistency equation of Lidsey et al. (1997)., Comment: 5 pages RevTeX

We investigate the prior dependence of constraints on cosmic tensor perturbations. Commonly imposed is the strong prior of the single-field inflationary consistency equation, relating the tensor spectral index nT to the tensor-to-scalar ratio r. Dropping it leads to significantly different constraints on nT, with both positive and negative values allowed with comparable likelihood, and substantially increases the upper limit on r on scales k = 0.01 Mpc^-1 to 0.05 Mpc^-1, by a factor of ten or more. Even if the consistency equation is adopted, a uniform prior on r on one scale does not correspond to a uniform one on another; constraints therefore depend on the pivot scale chosen. We assess the size of this effect and determine the optimal scale for constraining the tensor amplitude, both with and without the consistency relation., Comment: 14 pages, 6 figures. v2: added references. v3: minor clarifications; added reference; matches version accepted by JCAP