On the true nature of renormalizability in Horava-Lifshitz gravity

We argue that the true nature of the renormalizability of Horava-Lifshitz gravity lies in the presence of higher order spatial derivatives and not in the anisotropic Lifshitz scaling of space and time. We discuss the possibility of constructing a higher order spatial derivatives model that has the same renormalization properties of Horava-Lifshitz gravity but that does not make use of the Lifshitz scaling. In addition, the state-of-the-art of the Lorentz symmetry restoration in Horava-Lifshitz-type theories of gravitation is reviewed.Comment: Latex file in Revtex style, 5 pages, no figures. v2: references added, version accepted for publication in Foundations of Physic

First lattice QCD estimate of the g_{D^* D pi} coupling

We present the results of the first lattice QCD study of the strong coupling g_{D^* D pi}. From our simulations in the quenched approximation, we obtain g_{D^* D pi} = 18.8 +/- 2.3^{+1.1}_{-2.0} and hat(g)_c = 0.67 +/- 0.08^{+0.04}_{-0.06}. Whereas previous theoretical studies gave different predictions, our result favours a large value for hat(g)_c. It agrees very well with the recent experimental value by CLEO. hat(g) varies very little with the heavy mass and we find in the infinite mass limit hat(g)_infinity = 0.69(18).Comment: 24 pages, 7 figures; references added, corrected typos, Comments added about the continuum limi

Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte DNA

Background: Altered DNA methylation has been associated with various diseases. Objective: We evaluated the association between levels of methylation in leukocyte DNA at long interspersed nuclear element 1 (LINE-1) and genetic and non-genetic characteristics of 892 control participants from the Spanish Bladder Cancer/EPICURO study. Methods: We determined LINE-1 methylation levels by pyrosequencing. Individual data included demographics, smoking status, nutrient intake, toenail concentrations of 12 trace elements, xenobiotic metabolism gene variants, and 515 polymorphisms among 24 genes in the one-carbon metabolism pathway. To assess the association between LINE-1 methylation levels (percentage of methylated cytosines) and potential determinants, we estimated beta coefficients (βs) by robust linear regression. Results: Women had lower levels of LINE-1 methylation than men (β = –0.7, p = 0.02). Persons who smoked blond tobacco showed lower methylation than nonsmokers (β = –0.7, p = 0.03). Arsenic toenail concentration was inversely associated with LINE-1 methylation (β = –3.6, p = 0.003). By contrast, iron (β = 0.002, p = 0.009) and nickel (β = 0.02, p = 0.004) were positively associated with LINE-1 methylation. Single nucleotide polymorphisms (SNPs) in DNMT3A (rs7581217-per allele, β = 0.3, p = 0.002), TCN2 (rs9606756-GG, β = 1.9, p = 0.008; rs4820887-AA, β = 4.0, p = 4.8 × 10–7; rs9621049-TT, β = 4.2, p = 4.7 × 10–9), AS3MT (rs7085104-GG, β = 0.7, p = 0.001), SLC19A1 (rs914238, TC vs. TT: β = 0.5 and CC vs. TT: β = –0.3, global p = 0.0007) and MTHFS (rs1380642, CT vs. CC: β = 0.3 and TT vs. CC; β = –0.8, global p = 0.05) were associated with LINE-1 methylation. Conclusions: We identified several characteristics, environmental factors, and common genetic variants that predicted DNA methylation among study participants

A CRISPR-Cas9-engineered mouse model for GPI anchor deficiency mirrors human phenotype and shows hippocampal synaptic dysfunctions

Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency. Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol anchor pathway show cognitive impairments, a motor delay and in many cases epilepsy. Thus far, the pathophysiology underlying the disease remains unclear and suitable rodent models that mirror human pathophysiology have not been available. We therefore generated a mouse model using CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, at a site that is also conserved in mice, Pigv:c.1022C>A (p.A341E). Reflecting the human pathology mutant Pigv(341E) mice showed deficits in motor coordination and cognitive impairment with poorer long-term spatial memory than wild-type mice, as well as alterations in sociability and sleep patterns. Furthermore, immunohistochemistry showed decreased synaptophysin-immunoreactivity and electrophysiology recordings demonstrated reduced hippocampal synaptic transmission in Pigv(341E) mice that may underlie impaired memory formation. To gain a deeper and broader molecular understanding of the consequences of glycosylphosphatidylinositol anchor deficiency, we performed single-cell RNA sequencing on acutely isolated hippocampal cells of Pigv(341E) and wild-type mice. We found that hippocampal cells from adult Pigv(341E) mice exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction of Abl1 transcripts in several cell clusters suggests a link to the signaling pathway of glycosylphosphatidylinositol-anchored ephrins. We also observed increased levels of Hdc that might affect histamine metabolism with consequences in circadian rhythm. In summary, we present here the first mouse model with a patient-specific hypomorphic mutation that mirrors the human phenotype and shows a hippocampal synaptic defect. This new mouse model will not only open the doors for further investigation into the pathophysiology of glycosylphosphatidylinositol biosynthesis deficiency in future studies, but will also deepen our understanding in the role of glycosylphosphatidylinositol-anchor related pathways in brain development

Historical separation and present-day structure of common dolphinfish (Coryphaena hippurus) populations in the Atlantic Ocean and Mediterranean Sea

The common dolphinfish (Coryphaena hippurus) is an epipelagic, mid-trophic level, highly migratory species distributed throughout the world’s tropical and subtropical oceans in waters greater than 20C. Life-history variables, migratory behaviour, and genetic markers have been used to define major stocks in the central Atlantic Ocean and Mediterranean Sea. Here, we used the mitochondrial DNA gene NADH subunit 1 (688 bp) to test for differences between population groups. A total of 103 haplotypes were detected among 203 fish. Gene diversities in samples were large and similar among populations (mean h ¼ 0.932; range 0.894–0.987), but nucleotide diversities varied widely among samples (range p ¼ 0.004–0.034) and appear to reflect population histories. Principal component analysis revealed two large populations groups, and the analysis of molecular variation and pairwise values of UST resolved population structure within these groups. Populations in the eastern Atlantic and Mediterranean showed the largest amounts of divergence from one another (UCT ¼ 0.331). Adult movement and biophysical barriers to larval dispersal may explain contemporary differences between stocks, but the divergent populations in the Mediterranean Sea are likely due to isolations by cold temperature barriers during Pleistocene glaciations. The geographically large stock groupings require international cooperation in the harvest management and conservation of local dolphinfish populations

Angular momentum exchange during secular migration of two-planet systems

We investigate the secular dynamics of two-planet coplanar systems evolving under mutual gravitational interactions and dissipative forces. We consider two mechanisms responsible for the planetary migration: star-planet (or planet-satellite) tidal interactions and interactions of a planet with a gaseous disc. We show that each migration mechanism is characterized by a specific law of orbital angular momentum exchange. Calculating stationary solutions of the conservative secular problem and taking into account the orbital angular momentum leakage, we trace the evolutionary routes followed by the planet pairs during the migration process. This procedure allows us to recover the dynamical history of two-planet systems and constrain parameters of the involved physical processes.Comment: 20 pages, 9 figures, accepted for publication in Celestial Mechanics and Dynamical Astronomy (special issue on Exoplanets

Factors Associated with Mortality in Nosocomial Lower Respiratory Tract Infections : An ENIRRI Analysis

Nosocomial lower respiratory tract infections (nLRTIs) are associated with unfavorable clinical outcomes and significant healthcare costs. nLRTIs include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and other ICU-acquired pneumonia phenotypes. While risk factors for mortality in these infections are critical to guide preventive strategies, it remains unclear whether they vary based on their requirement of invasive mechanical ventilation (IMV) at any point during the hospitalization. This study aims to identify risk factors associated with short- and long-term mortality in patients with nLRTIs, considering differences between those requiring IMV and those who do not. This multinational prospective cohort study included ICU-admitted patients diagnosed with nLRTI from 28 hospitals across 13 countries in Europe and South America between May 2016 and August 2019. Patients were selected based on predefined inclusion and exclusion criteria, and clinical data were collected from medical records. A random forest classifier determined the most optimal clustering strategy when comparing pneumonia site acquisition [ward or intensive care unit (ICU)] versus intensive mechanical ventilation (IMV) necessity at any point during hospitalization to enhance the accuracy and generalizability of the regression models. A total of 1060 patients were included. The random forest classifier identified that the most efficient clustering strategy was based on ventilation necessity. In total, 76.4% of patients [810/1060] received IMV at some point during the hospitalization. Diabetes mellitus was identified to be associated with 28-day mortality in the non-IMV group (OR [IQR]: 2.96 [1.28-6.80], p = 0.01). The 90-day mortality-associated factor was MDRP infection (1.98 [1.13-3.44], p = 0.01). For ventilated patients, chronic liver disease was associated with 28-day mortality (2.38 [1.06-5.31] p = 0.03), with no variable showing statistical and clinical significance at 90 days. The risk factors associated with 28-day mortality differ from those linked to 90-day mortality. Additionally, these factors vary between patients receiving invasive mechanical ventilation and those in the non-invasive ventilation group. This underscores the necessity of tailoring therapeutic objectives and preventive strategies with a personalized approach

Multilayer nanocarrier for the codelivery of interferons: a promising strategy for biocompatible and long-acting antiviral treatment

BACKGROUND: Interferons (IFNs) are cytokines involved in the immune response with a synergistic regulatory effect on the immune response. They are therapeutics for various viral and proliferative conditions, with proven safety and efficacy. Their clinical application is challenging due to the molecules’ size, degradation, and pharmacokinetics. We are working on new drug delivery systems that provide adequate therapeutic concentrations for these cytokines and prolong their half-life in the circulation, such as nanoformulations. METHODS: Through nanoencapsulation using electrospray technology and biocompatible and biodegradable polymers, we are developing a controlled release system based on nanoparticles for viral infections of the respiratory tract. RESULTS: We developed a controlled release system for viral respiratory tract infections. A prototype nanoparticle with a core was created, which hydrolyzed the polyvinylpyrrolidone (PVP) shell , releasing the active ingredients interferon-alpha (IFN-α) and interferon-gamma (IFN-γ). The chitosan (QS) core degraded slowly, with a controlled release of IFN-α. The primary and rapid effect of the interferon combination ensured an antiviral and immunoregulatory response from day one, induced by IFN-α and enhanced by IFN-γ. The multilayer design demonstrated an optimal toxicity profile. CONCLUSIONS: This formulation is an inhaled dry powder intended for the non-invasive intranasal route. The product does not require a cold chain and has the potential for self-administration in the face of emerging viral infections. This novel drug has applications in multiple infectious, oncological, and autoimmune conditions, and further development is proposed for its therapeutic potential. This prototype would ensure greater bioavailability, controlled release, fewer adverse effects, and robust biological action through the simultaneous action of both molecules

Elastic differential cross-section dσ/dt at s√=2.76 TeV and implications on the existence of a colourless C-odd three-gluon compound state

The proton–proton elastic differential cross section dσ/dt has been measured by the TOTEM experiment at s√=2.76 TeV energy with β∗=11 m beam optics. The Roman Pots were inserted to 13 times the transverse beam size from the beam, which allowed to measure the differential cross-section of elastic scattering in a range of the squared four-momentum transfer (|t|) from 0.36 to 0.74 GeV2. The differential cross-section can be described with an exponential in the |t|-range between 0.36 and 0.54 GeV2, followed by a diffractive minimum (dip) at |tdip|=(0.61±0.03) GeV2 and a subsequent maximum (bump). The ratio of the dσ/dt at the bump and at the dip is 1.7±0.2. When compared to the proton–antiproton measurement of the D0 experiment at s√=1.96 TeV, a significant difference can be observed. Under the condition that the effects due to the energy difference between TOTEM and D0 can be neglected, the result provides evidence for the exchange of a colourless C-odd three-gluon compound state in the t-channel of the proton–proton and proton–antiproton elastic scattering