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Holography has provided valuable insights into the time evolution of strongly coupled gauge theories in a fixed spacetime. However, this framework is insufficient if this spacetime is dynamical. We present a scheme to evolve a four-dimensional, strongly interacting gauge theory coupled to four-dimensional dynamical gravity in the semiclassical regime. As in previous work, we use holography to evolve the quantum gauge theory stress tensor, whereas the four-dimensional metric evolves according to Einstein’s equations coupled to the expectation value of the stress tensor. The novelty of our approach is that both the boundary and the bulk spacetimes are constructed dynamically, one time step at a time. We focus on Friedmann-Lemaître-Robertson-Walker geometries and evolve far-from-equilibrium initial states that lead to asymptotically expanding, flat or collapsing Universes.
Using full 3+1 dimensional general-relativistic hydrodynamic simulations of equal- and unequal-mass neutron-star binaries with properties that are consistent with those inferred from the inspiral of GW170817, we perform a detailed study of the quark-formation processes that could take place after merger. We use three equations of state consistent with current pulsar observations derived from a novel finite-temperature framework based on V-QCD, a non-perturbative gauge/gravity model for Quantum Chromodynamics. In this way, we identify three different post-merger stages at which mixed baryonic and quark matter, as well as pure quark matter, are generated. A phase transition triggered collapse already ≲10ms after the merger reveals that the softest version of our equations of state is actually inconsistent with the expected second-long post-merger lifetime of GW170817. Our results underline the impact that multi-messenger observations of binary neutron-star mergers can have in constraining the equation of state of nuclear matter, especially in its most extreme regimes.
Using full 3+1 dimensional general-relativistic hydrodynamic simulations of equal- and unequal-mass neutron-star binaries with properties that are consistent with those inferred from the inspiral of GW170817, we perform a detailed study of the quark-formation processes that could take place after merger. We use three equations of state consistent with current pulsar observations derived from a novel finite-temperature framework based on V-QCD, a non-perturbative gauge/gravity model for Quantum Chromodynamics. In this way, we identify three different post-merger stages at which mixed baryonic and quark matter, as well as pure quark matter, are generated. A phase transition triggered collapse already ≲ 10 ms after the merger reveals that the softest version of our equations of state is actually inconsistent with the expected second-long post-merger lifetime of GW170817. Our results underline the impact that gravitational wave observations of binary neutron-star mergers can have in constraining the equation of state of nuclear matter, especially in its most extreme regimes.
We present a novel framework for the equation of state of dense and hot quantum chromodynamics (QCD), which focuses on the region of the phase diagram relevant for neutron star mergers and core-collapse supernovae. The model combines predictions from the gauge/gravity duality with input from lattice field theory, QCD perturbation theory, chiral effective theory, and statistical modeling. It is therefore, by construction, in good agreement with theoretical constraints both at low and high densities and temperatures. The main ingredients of our setup are the nonperturbative V-QCD model based on the gauge/gravity duality, a van der Waals model for nucleon liquid, and the DD2 version of the Hempel-Schaffner-Bielich statistical model of nuclear matter. By consistently combining these models, we also obtain a description for the nuclear to quark matter phase transition and its critical end point. The parameter dependence of the model is represented by three (soft, intermediate, and stiff) variants of the equation of state, all of which agree with observational constraints from neutron stars and their mergers. We discuss resulting constraints for the equation of state, predictions for neutron stars, and the location of the critical point.
Holography has provided valuable insights into the time evolution of strongly coupled gauge theories in a fixed spacetime. However, this framework is insufficient if this spacetime is dynamical. We present a scheme to evolve a four-dimensional, strongly interacting gauge theory coupled to four-dimensional dynamical gravity in the semiclassical regime. As in previous work, we use holography to evolve the quantum gauge theory stress tensor, whereas the four-dimensional metric evolves according to Einstein's equations coupled to the expectation value of the stress tensor. The novelty of our approach is that both the boundary and the bulk spacetimes are constructed dynamically, one time step at a time. We focus on Friedmann-Lemaître-Robertson-Walker geometries and evolve far-from-equilibrium initial states that lead to asymptotically expanding, flat or collapsing Universes.
The epitranscriptome embodies many new and largely unexplored functions of RNA. A major roadblock in the epitranscriptomics field is the lack of transcriptome-wide methods to detect more than a single RNA modification type at a time, identify RNA modifications in individual molecules, and estimate modification stoichiometry accurately. We address these issues with CHEUI (CH3 (methylation) Estimation Using Ionic current), a new method that concurrently detects N6-methyladenosine (m6A) and 5-methylcytidine (m5C) in individual RNA molecules from the same sample, as well as differential methylation between any two conditions. CHEUI processes observed and expected nanopore direct RNA sequencing signals with convolutional neural networks to achieve high single-molecule accuracy and outperforms other methods in detecting m6A and m5C sites and quantifying their stoichiometry. CHEUI’s unique capability to identify two modification types in the same sample reveals a non-random co-occurrence of m6A and m5C in mRNA transcripts in cell lines and tissues. CHEUI unlocks an unprecedented potential to study RNA modification configurations and discover new epitranscriptome functions.
The epitranscriptome embodies many new and largely unexplored functions of RNA. A major roadblock in the epitranscriptomics field is the lack of transcriptome-wide methods to detect more than a single RNA modification type at a time, identify RNA modifications in individual molecules, and estimate modification stoichiometry accurately. We address these issues with CHEUI (CH3 (methylation) Estimation Using Ionic current), a new method that concurrently detects N6-methyladenosine (m6A) and 5-methylcytidine (m5C) in individual RNA molecules from the same sample, as well as differential methylation between any two conditions, using signals from nanopore direct RNA sequencing. CHEUI processes observed and expected signals with convolutional neural networks to achieve high single-molecule accuracy and outperform other methods in detecting m6A and m5C sites and quantifying their stoichiometry. CHEUI’s unique capability to identify two modification types in the same sample reveals a non-random co-occurrence of m6A and m5C in mRNA transcripts in cell lines and tissues. CHEUI unlocks an unprecedented potential to study RNA modification configurations and discover new epitranscriptome functions.
The expanding field of epitranscriptomics might rival the epigenome in the diversity of the biological processes impacted. However, the identification of modifications in individual RNA molecules remains challenging. We present CHEUI, a new method that detects N6-methyladenosine (m6A) and 5-methylcytidine (m5C) at single-nucleotide and single-molecule resolution from Nanopore signals. CHEUI predicts methylation in Nanopore reads and transcriptomic sites in a single condition, and differential m6A and m5C methylation between any two conditions. Using extensive benchmarking with Nanopore data derived from synthetic and natural RNA, CHEUI showed higher accuracy than other existing methods in detecting m6A and m5C sites and quantifying the site stoichiometry levels, while maintaining a lower proportion of false positives. CHEUI provides a new capability to detect RNA modifications with high accuracy and resolution that can be cost-effectively expanded to other modifications to unveil the full span of the epitranscriptome in normal and disease conditions.
Objective: Skin and soft tissue infections (SSTI) are a commonly known entity of diseases associated with difficult treatment procedures. The current gold standard when there is a rapidly progressing infection of soft tissues with a risk of sepsis is radical surgical debridement accompanied by systemic antibiotic therapy. In clinical settings, local antibiotics alone or formulated within carrier material are commonly used alongside this therapy regimen. One possibility of local antibiotic application is the fixation of colistin with fibrin glue spray. It is not yet sufficiently researched how the local antibiotic concentrations remain as high as possible over time.
Methods: We conducted an animal study including 29 male Wistar rats inducing sterile back sores reaching the muscle fascia. We sprayed only colistin, simultaneously or consecutively, with fibrin glue in different groups in order to measure the tissue concentration of the antibiotic applied locally.
Results: After liquid chromatography and quadrupole mass spectrometry analysis, it could be demonstrated that in comparison to the colistin group, tissue concentrations of colistin stayed significantly higher in the wound tissue when it was fixed with fibrin glue. This was observed in both groups, the simultaneous as well as in the consecutively fibrin glue sprayed groups after colistin application.
Conclusion: The fixation of colistin with the fibrin-glue-spray technique as a carrier for local antibiotic therapy is an easy and inexpensive method and shows promising potential for the treatment of SSTI.
Hearing loss in old age, which often goes untreated, has far-reaching consequences. Furthermore, reduction of cognitive abilities and dementia can also occur, which also affects quality of life. The aim of this study was to investigate the hearing performance of seniors without hearing complaints with respect to speech perception in noise and the ability to localize sounds. Results were tested for correlations with age and cognitive performance. The study included 40 subjects aged between 60 and 90 years (mean age: 69.3 years) with not self-reported hearing problems. The subjects were screened for dementia. Audiological tests included pure-tone audiometry and speech perception in two types of background noise (continuous and amplitude-modulated noise) which was either co-located or spatially separated (multi-source noise field, MSNF) from the target speech. Sound localization ability was assessed and hearing performance was self-evaluated by a questionnaire. Speech in noise and sound localization was compared with young normal hearing adults. Although considering themselves as hearing normal, 17 subjects had at least a mild hearing loss. There was a significant negative correlation between hearing loss and dementia screening (DemTect) score. Speech perception in noise decreased significantly with age. There were significant negative correlations between speech perception in noise and DemTect score for both spatial configurations. Mean SRTs obtained in the co-located noise condition with amplitude-modulated noise were on average 3.1 dB better than with continuous noise. This gap-listening effect was severely diminished compared to a younger normal hearing subject group. In continuous noise, spatial separation of speech and noise led to better SRTs compared to the co-located masker condition. SRTs in MSNF deteriorated in modulated noise compared to continuous noise by 2.6 dB. Highest impact of age was found for speech perception scores using noise stimuli with temporal modulation in binaural test conditions. Mean localization error was in the range of young adults. Mean amount of front/back confusions was 11.5% higher than for young adults. Speech perception tests in the presence of temporally modulated noise can serve as a screening method for early detection of hearing disorders in older adults. This allows for early prescription of hearing aids.