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Abstract In this work, we study the realization of non-invertible duality symmetries along the toroidal branch of the c = 2 conformal manifold. A systematic procedure to construct symmetry defects is implemented to show that all Rational Conformal Field Theories along this branch enjoy duality symmetries. Furthermore, we delve into an in-depth analysis of two representative cases of multicritical theories, where the toroidal branch meets various orbifold branches. For these particular examples, the categorical data and the defect Hilbert spaces associated with the duality symmetries are obtained by resorting to modular covariance. Finally, we study the interplay between these novel symmetries and the various exactly marginal and relevant deformations, including some representative examples of Renormalization Group flows where the infrared is constrained by the non-invertible symmetries and their anomalies.

Abstract We study orientifold projections of families of four-dimensional N $$ \mathcal{N} $$ = 1 toric quiver gauge theories. We restrict to quivers that have the unusual property of being associated with multiple periodic planar diagrams which give rise, in general, to inequivalent models. A suitable orientifold projection relates a subfamily of the latter by conformal duality. That is, there exist exactly marginal deformations that connect the projected models. The deformations take the form of a sign flip in some of the superpotential interactions, similarly to the β-deformation of N $$ \mathcal{N} $$ = 4 SYM. Our construction generalizes previous results on the orientifold projections of the PdP3b and PdP3c singularities.

Abstract We study various orientifold projections of 4d N $$ \mathcal{N} $$ = 1 toric gauge theories, associated with CY singularities known as L a,b,a /ℤ2, with a + b even. We obtain superconformal chiral theories that have the same central charge, anomalies and superconformal index, whereas they were different before the orientifold. Some of these projections are implemented by a novel type of orientifold without fixed loci, known as glide orientifold. We claim that these theories flow to the same conformal manifold, and they are connected by quadratic exactly marginal deformations. The latter can be written in terms of conjugate pairs of bifundamental fields of R-charge one, generalizing previous results for unoriented non-chiral theories.

Electromagnetic transients known as kilonovae (KN), are among the photonic messengers released in the post-merger phase of compact binary objects, for example, binary neutron stars, and they have been recently observed as the electromagnetic counterpart of related gravitational-wave (GW) events. Detection of the KN signal plays a fundamental role in the multi-messenger astronomy entering in a sophisticated GW-detecting network. The KN light curve also delivers precious information on the composition and dynamics of the neutron-rich post-merger plasma ejecta (relying on r-process nucleosynthesis yields). In this sense, studying KN becomes of great relevance for nuclear astrophysics. Because of the highly heterogeneous composition, plasma opacity has a great impact both on radiative transport and spectroscopic observation of KN. Theoretical models attempting in encoding the opacity of this system often fail, due to the complexity of blending plethora of both light- and heavy-r nuclei transition lines, requesting for more complete atomic database. Trapped magneto-plasmas conceived in PANDORA could answer to these requests, allowing experimental in-laboratory measurements of optical properties and opacities, at plasma electron densities and temperatures resembling early-stage plasma ejecta’s conditions, contributing to shed light on r-process metallic species abundance at the blue-KN diffusion time. A numerical study has been recently performed, supporting the choice of first physics cases to be investigated and the design of the experimental setup. In this article, we report on the feasibility of metallic plasmas on the basis of the results from the systematic numerical survey on optical spectra computed under non-local thermodynamic equilibrium (NLTE) for several light-r nuclei. Results show the great impact of the NLTE regime of laboratory magneto-plasmas on the gray opacity contribution contrasted with those under the astrophysical LTE assumption. A first experimental attempt of reproducing ejecta plasma conditions has been performed on the operative Flexible Plasma Trap (FPT) at the INFN-LNS and here presented, together with first plasma characterization of density and temperature, via non-invasive optical emission spectroscopy (OES). The measured plasma parameters have supported numerical simulations to explore optical properties of NLTE gaseous and metallic plasmas, in view of the near-future plasma opacity measurements through spectroscopic techniques. The novel work so far performed on these under-dense and low-temperature magneto-plasmas, opens the route for the first-time to future in-laboratory plasma opacity measurements of metallic plasma species relevant for KN light curve studies.

We study the orientifold of the N=1 superconformal field theories describing D3-branes probing the Suspended Pinch Point singularity, as well as the orientifolds of non-chiral theories obtained by a specific orbifold Zn of SPP. We find that these models realize a mechanism analogous to the one recently found for the orientifold of the complex Calabi-Yau cone over the Pseudo del Pezzo surface PdP3c: they all flow to a new IR fixed point such that the value of the a-charge is less than half the one of the oriented theory. We also find that the value of a coincides with the charge of specific orientifolds of the toric singularities L(n¯,n¯,n¯) with n¯=3n/2 for n even or L(n¯,n¯+1,n¯) with n¯=(3n−1)/2 for n odd, suggesting the existence of an IR duality.

Abstract We study the interplay between mass deformations and unoriented projections of super-conformal quiver gauge theories resulting from D3-branes at (toric) Calabi-Yau singularities. We focus on simple orbifold cases (ℂ3/ℤ3 and ℂ3/ℤ4) and their non-orbifold descendants. This allows us to generalize the construction rules and clarify points that have been previously overlooked. In particular we spell out the conditions of anomaly cancellations as well as super-conformal invariance that typically require the introduction of flavour branes, which in turn may spoil toric symmetry. Finally, we discuss duality cascades in this context and the interplay between Seiberg/toric duality and unoriented projection with (or without) mass deformations.

We study the orientifold projections of the N=1 superconformal field theories describing D3-branes probing the Pseudo del Pezzo singularities PdP3b and PdP3c. The PdP3c parent theory admits two inequivalent orientifolds. Exploiting a maximization, we find that one of the two has an a-charge smaller than what one would expect from the orientifold projection, which suggests that the theory flows to the fixed point in the infrared. Surprisingly, the value of a coincides with the charge of the unoriented PdP3b and we interpret this as the sign of an infrared duality.

Sounding balloons, available at very low cost from commercial vendors and operable with minimal training, have an excellent potential as testing platforms in the near-space environment. The work reported here was motivated by the need to perform an experimental assessment of the radio frequency (RF) background present in the ISM (Industrial, Scientific and Medical) bands, namely 868 MHz (Ultra High Frequency—UHF) and 2.4 GHz (S-Band), simulating the operational environment of a Low Earth Orbit (LEO) constellation forInternet of Things (IoT) telecommunications. To this end, five balloons were flown with a dedicated RF payload. Along with the radio measurements, the flights provided a convenient opportunity to collect data on the dynamic behavior of the payload gondola. We report on the system design and the operational phase of the mission, and discuss the data collected throughout the successful flight campaign. As a result, a preliminary understanding of the gondola dynamics has been gained, including both linear accelerations and attitude oscillations. It is also concluded that the two ISM bands considered are actually suitable for IoT ground-to-LEO links.

Sin resumen

Angiotensin I converting enzyme (ACE1) maintains blood pressure homeostasis by converting angiotensin I into angiotensin II in the renin-angiotensin system (RAS). ACE1 is expressed in the brain, where an intrinsic RAS regulates complex cognitive functions including learning and memory. ACE1 has been implicated in neurodegenerative disorders including Alzheimer's disease and Parkinson's disease, but the mechanisms remain incompletely understood. Here, we performed single-nucleus RNA sequencing to characterize the expression of RAS genes in the hippocampus and discovered that Ace is mostly expressed in CA1 region excitatory neurons. To gain a deeper understanding of the function of neuronal ACE1, we generated ACE1 conditional knockout (cKO) mice lacking ACE1 expression specifically in hippocampal and cortical excitatory neurons. ACE1 cKO mice exhibited hippocampus-dependent memory impairment in the Morris water maze, y-maze, and fear conditioning tests. Total ACE1 level was significantly reduced in the cortex and hippocampus of ACE1 cKO mice showing that excitatory neurons are the predominant cell type expressing ACE1 in the forebrain. Despite similar reductions in total ACE1 level in both the hippocampus and cortex, the RAS pathway was dysregulated in the hippocampus only. Importantly, ACE1 cKO mice exhibited age-related capillary loss selectively in the hippocampus. Here, we show selective vulnerability of the hippocampal microvasculature and RAS pathway to neuronal ACE1 knockout. Our results provide important insights into the function of ACE1 in the brain and demonstrate a connection between neuronal ACE1 and cerebrovascular function in the hippocampus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Healthcare-associated infections (HAIs) have a significant impact on patients' morbidity and mortality, and have a detrimental financial impact on the healthcare system. Various strategies exist to prevent HAIs, but economic evaluations are needed to determine which are most appropriate., Aim: To present the financial impact of a nationwide project on HAI prevention in intensive care units (ICUs) using a quality improvement (QI) approach., Methods: A health economic evaluation assessed the financial results of the QI initiative 'Saúde em Nossas Mãos' (SNM), implemented in Brazil between January 2018 and December 2020. Among 116 participating institutions, 13 (11.2%) fully reported the aggregate cost and stratified patients (with vs without HAIs) in the pre-intervention and post-intervention periods. Average cost (AC) was calculated for each analysed HAI: central-line-associated bloodstream infections (CLABSIs), ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infections (CAUTIs). The absorption model and time-driven activity-based costing were used for cost estimations. The numbers of infections that the project could have prevented during its implementation were estimated to demonstrate the financial impact of the SNM initiative., Results: The aggregated ACs calculated for each HAI from these 13 ICUs - US$8480 for CLABSIs, US$10,039 for VAP, and US$7464 for CAUTIs - were extrapolated to the total number of HAIs prevented by the project (1727 CLABSIs, 3797 VAP and 2150 CAUTIs). The overall savings of the SNM as of December 2020 were estimated at US$68.8 million, with an estimated return on investment (ROI) of 765%., Conclusion: Reporting accurate financial data on HAI prevention strategies is still challenging in Brazil. These results suggest that a national QI initiative to prevent HAIs in critical care settings is a feasible and value-based approach, reducing financial waste and yielding a significant ROI for the healthcare system., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Current scientific research is driven by the ability to manipulate gene expression by utilizing the Cre/loxP system in transgenic mouse models. However, artifacts in Cre-driver mouse lines that introduce undesired effects and confound results are increasingly being reported. Here, we show aberrant neuroinflammation and synaptic changes in two widely used Cre-driver mouse models. Neuroinflammation in CaMKIIα-iCre mice was characterized by the activation and proliferation of microglia and astrocytes in synaptic layers of the hippocampus. Increased GFAP and Iba1 levels were observed in hippocampal brain regions of 4-, 8- and 22-month-old CaMKIIα-iCre mice compared to WT littermates. Synaptic changes in NMDAR, AMPAR, PSD95 and phosphorylated CaMKIIα became apparent in 8-month-old CaMKIIα-iCre mice but were not observed in 4-month-old CaMKIIα-iCre mice. Synaptophysin and synaptoporin were unchanged in CaMKIIα-iCre compared to WT mice, suggesting that synaptic alterations may occur in excitatory postsynaptic regions in which iCre is predominantly expressed. Finally, hippocampal volume was reduced in 22-month-old CaMKIIα-iCre mice compared to WT mice. We tested the brains of mice of additional common Cre-driver mouse models for neuroinflammation; the nestin-Cre mouse model showed synaptic changes and astrocytosis marked by increased GFAP+ astrocytes in cortical and hippocampal regions, while the original CaMKIIα-Cre T29-1 strain was comparable to WT mice. The mechanisms underlying abnormal neuroinflammation in nestin-Cre and CaMKIIα-iCre are unknown but may be associated with high levels of Cre expression. Our findings are critical to the scientific community and demonstrate that the correct Cre-driver controls must be included in all studies using these mice., (© 2022. The Author(s).)

Background: Amyloid plaque deposition and axonal degeneration are early events in AD pathogenesis. Aβ disrupts microtubules in presynaptic dystrophic neurites, resulting in the accumulation of impaired endolysosomal and autophagic organelles transporting β-site amyloid precursor protein cleaving enzyme (BACE1). Consequently, dystrophic neurites generate Aβ42 and significantly contribute to plaque deposition. Farnesyltransferase inhibitors (FTIs) have recently been investigated for repositioning toward the treatment of neurodegenerative disorders and block the action of farnesyltransferase (FTase) to catalyze farnesylation, a post-translational modification that regulates proteins involved in lysosome function and microtubule stability. In postmortem AD brains, FTase and its downstream signaling are upregulated. However, the impact of FTIs on amyloid pathology and dystrophic neurites is unknown., Methods: We tested the effects of the FTIs LNK-754 and lonafarnib in the 5XFAD mouse model of amyloid pathology., Results: In 2-month-old 5XFAD mice treated chronically for 3 months, LNK-754 reduced amyloid plaque burden, tau hyperphosphorylation, and attenuated the accumulation of BACE1 and LAMP1 in dystrophic neurites. In 5-month-old 5XFAD mice treated acutely for 3 weeks, LNK-754 reduced dystrophic neurite size and LysoTracker-Green accumulation in the absence of effects on Aβ deposits. Acute treatment with LNK-754 improved memory and learning deficits in hAPP/PS1 amyloid mice. In contrast to LNK-754, lonafarnib treatment was less effective at reducing plaques, tau hyperphosphorylation and dystrophic neurites, which could have resulted from reduced potency against FTase compared to LNK-754. We investigated the effects of FTIs on axonal trafficking of endolysosomal organelles and found that lonafarnib and LNK-754 enhanced retrograde axonal transport in primary neurons, indicating FTIs could support the maturation of axonal late endosomes into lysosomes. Furthermore, FTI treatment increased levels of LAMP1 in mouse primary neurons and in the brains of 5XFAD mice, demonstrating that FTIs stimulated the biogenesis of endolysosomal organelles., Conclusions: We show new data to suggest that LNK-754 promoted the axonal trafficking and function of endolysosomal compartments, which we hypothesize decreased axonal dystrophy, reduced BACE1 accumulation and inhibited amyloid deposition in 5XFAD mice. Our results agree with previous work identifying FTase as a therapeutic target for treating proteinopathies and could have important therapeutic implications in treating AD., (© 2022. The Author(s).)

Dengue virus (DENV) is a flavivirus responsible for the most common and burdensome arthropod-borne viral disease of humans[1]. DENV evolution has been extensively studied on broad geographic and time scales, using sequences from a single gene[2,3]. It is believed that DENV evolution in humans is dominated primarily by purifying selection due to the constraint of maintaining fitness in both humans and mosquitoes[4,5]. Few studies have explored DENV evolutionary dynamics using whole genome sequences, nor have they explored changes in viral diversity that occur during intra-epidemic periods. We used deep sequencing of the viral coding region to characterize DENV-1 evolution in a Colombian population sampled during two high-prevalence dengue seasons in which serotype dominance shifted. Our data demonstrate patterns of strain extinction and replacement within DENV-1 as its prevalence waned and DENV-3 became established. A comparison of whole-genome versus single-gene-based phylogenetic analyses highlights an important difference in evolutionary patterns. We report a trend of higher nonsynonymous to synonymous diversity ratios among non-structural (NS) genes, and statistically significantly higher values among these ratios in the NS1 gene after DENV-1 strain replacement. These results suggest that positive selection could be driving DENV evolution within individual communities. Signals of positive selection coming from distinct samples may be drowned out when combining multiple regions with differing patterns of endemic transmission as commonly done by large-scale geo-temporal assessments. Here, we frame our findings within a small, local transmission history which aids significance. Moreover, these data suggest that the NS1 gene, rather than the E gene, may be a target of positive selection, although not mutually exclusive, and potentially useful sentinel of adaptive changes at the population level., Competing Interests: The authors have declared that no competing interests exist.

Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever. Since its recent emergence in 2014 in the American continent, ZIKV infection during pregnancy has been closely associated with a wide range of congenital abnormalities. To date, no vaccines or antivirals are publicly available. We developed Zika virus-like particles (VLPs) and evaluated their immunogenicity and protective efficacy in mouse models. ZIKV VLPs (ZIKVLPs) formulated with alum were injected into 6-8-week-old interferon deficient AG129 mice as well as wild type BALB/c mice. Control mice received PBS/alum. Animals were challenged with 200 PFU (>1000 AG129 LD50s) of ZIKV strain H/PF/2013. All vaccinated mice survived with no morbidity or weight loss while control animals either died at 9 days post challenge (AG129) or had increased viremia (BALB/c). Neutralizing antibodies were observed in all ZIKVLP vaccinated mice. The role of neutralizing antibodies in protecting mice was demonstrated by passive transfer. Our findings demonstrate the protective efficacy of the ZIKVLP vaccine and highlight the important role that neutralizing antibodies play in protection against ZIKV infection.