Observation of electroweak production of two jets in association with an isolated photon and missing transverse momentum, and search for a Higgs boson decaying into invisible particles at 13 TeV with the ATLAS detector

This paper presents a measurement of the electroweak production of two jets in association with a Zγ pair, with the Z boson decaying into two neutrinos. It also presents a search for invisible or partially invisible decays of a Higgs boson with a mass of 125 GeV produced through vector-boson fusion with a photon in the final state. These results use data from LHC proton–proton collisions at s√ = 13 TeV collected with the ATLAS detector and corresponding to an integrated luminosity of 139 fb−1. The event signature, shared by all benchmark processes considered for the measurements and searches, is characterized by a significant amount of unbalanced transverse momentum and a photon in the final state, in addition to a pair of forward jets. Electroweak Zγ production in association with two jets is observed in this final state with a significance of 5.2 (5.1 expected) standard deviations. The measured fiducial cross-section for this process is 1.31±0.29 fb. An observed (expected) upper limit of 0.37 (0.34+0.15−0.10) at 95% confidence level is set on the branching ratio of a 125 GeV Higgs boson to invisible particles, assuming the Standard Model production cross-section. The signature is also interpreted in the context of decays of a Higgs boson into a photon and a dark photon. An observed (expected) 95% CL upper limit on the branching ratio for this decay is set at 0.018 (0.017+0.007−0.005), assuming the Standard Model production cross-section for a 125 GeV Higgs boson

Constraints on Higgs boson properties using W W ∗(→ eνμν) jj production in 36.1 fb−1 of √s = 13 TeV pp collisions with the ATLAS detector

This article presents the results of two studies of Higgs boson properties using the WW∗(→eνμν)jj final state, based on a dataset corresponding to 36.1fb−1 of s√=13 TeV proton–proton collisions recorded by the ATLAS experiment at the Large Hadron Collider. The first study targets Higgs boson production via gluon–gluon fusion and constrains the CP properties of the effective Higgs–gluon interaction. Using angular distributions and the overall rate, a value of tan(α)=0.0±0.4(stat.)±0.3(syst.) is obtained for the tangent of the mixing angle for CP-even and CP-odd contributions. The second study exploits the vector-boson fusion production mechanism to probe the Higgs boson couplings to longitudinally and transversely polarised W and Z bosons in both the production and the decay of the Higgs boson; these couplings have not been directly constrained previously. The polarisation-dependent coupling-strength scale factors are defined as the ratios of the measured polarisation-dependent coupling strengths to those predicted by the Standard Model, and are determined using rate and kinematic information to be aL=0.91+0.10−0.18(stat.)+0.09−0.17(syst.) and aT=1.2±0.4(stat.)+0.2−0.3(syst.). These coupling strengths are translated into pseudo-observables, resulting in κVV=0.91+0.10−0.18(stat.)+0.09−0.17(syst.) and ϵVV=0.13+0.28−0.20 (stat.)+0.08−0.10(syst.). All results are consistent with the Standard Model predictions

Targeted metabolomic profiling in rat tissues reveals sex differences

Sex differences affect several diseases and are organ-and parameter-specific. In humans and animals, sex differences also influence the metabolism and homeostasis of amino acids and fatty acids, which are linked to the onset of diseases. Thus, the use of targeted metabolite profiles in tissues represents a powerful approach to examine the intermediary metabolism and evidence for any sex differences. To clarify the sex-specific activities of liver, heart and kidney tissues, we used targeted metabolomics, linear discriminant analysis (LDA), principal component analysis (PCA), cluster analysis and linear correlation models to evaluate sex and organ-specific differences in amino acids, free carnitine and acylcarnitine levels in male and female Sprague-Dawley rats. Several intra-sex differences affect tissues, indicating that metabolite profiles in rat hearts, livers and kidneys are organ-dependent. Amino acids and carnitine levels in rat hearts, livers and kidneys are affected by sex: male and female hearts show the greatest sexual dimorphism, both qualitatively and quantitatively. Finally, multivariate analysis confirmed the influence of sex on the metabolomics profiling. Our data demonstrate that the metabolomics approach together with a multivariate approach can capture the dynamics of physiological and pathological states, which are essential for explaining the basis of the sex differences observed in physiological and pathological conditions

Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma

In this work, multifunctional lipid nanocapsules (M-LNC) were designed to combine the activity of the cytotoxic drug paclitaxel (PTX) with the immunostimulant CpG. This nanosystem, consisting of modified lipid nanocapsules coated with a cationic polymeric shell composed of chitosan (CS), was able to allocate the hydrophobic drug PTX in the inner oily core, and to associate onto the surface the genetic material CpG. The CS-coated LNC (CS-LNC), showed a narrow size distribution with an average size of 70nm and a positive zeta potential (+25mV). They encapsulated PTX in a high amount (98%), and, due to the cationic surface charge, were able to adsorb CpG without losing stability. As a preliminary in vitro study, the apoptotic effect on GL261 glioma cells was investigated. The drug-loaded CS-LNC exhibited the ability to interact with glioma cells and induce an important apoptotic effect in comparison with blank systems. Finally, the M-LNC made of CS-LNC loaded with both CpG and PTX were tested in vivo, injected via convention enhanced delivery (CED) in GL261-glioma-bearing mice. The results showed that the overall survival of mice treated with the M-LNC was significantly increased in comparison with the control, Taxol(®), or the separated injection of PTX-loaded LNC and CpG. This effect was also confirmed by magnetic resonance imaging (MRI) which revealed the reduction of tumor growth in the animals treated with CpG and PTX-loaded M-LNC. All these findings suggested that the developed M-LNC could potentiate both CpG immunopotency and PTX antitumor activity by enhancing its delivery into the tumor microenvironment

Modeling nigrostriatal degeneration in organotypic cultures, a new ex vivo model of Parkinson’s disease

Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder afflicting 2% of the population older than 65 years worldwide. Recently, brain organotypic slices have been used to model neurodegenerative disorders, including PD. They conserve brain three-dimensional architecture, synaptic connectivity and its microenvironment. This model has allowed researchers a simple and rapid method to observe cellular interactions and mechanisms. In the present study, we developed an organotypic PD model from rat brains that includes all the areas involved in the nigrostriatal pathway in a single slice preparation, without using neurotoxins to induce the dopaminergic lesion. The mechanical transection of the nigrostriatal pathway obtained during slice preparation induced PD-like histopathology. Progressive nigrostriatal degeneration was monitored combining innovative approaches, such as diffusion tensor magnetic resonance imaging (DT-RMI) to follow fiber degeneration and mass spectrometry to quantify striatal dopamine content, together with bright-field and fluorescence microscopy imaging. A substantia nigra dopaminergic cell number decrease was observed by immunohistochemistry against rat tyrosine hydroxylase (TH) reaching 80% after 2 days in culture associated with a 30% decrease of striatal TH-positive fiber density, a 15% loss of striatal dopamine content quantified by mass spectrometry and a 70% reduction of nigrostriatal fiber fractional anisotropy quantified by DT-RMI. In addition, a significant decline of medium spiny neuron density was observed from days 7 to 16. These sagittal organotypic slices could be used to study the early stage of PD, namely dopaminergic degeneration, and the late stage of the pathology with dopaminergic and GABAergic neuron loss. This novel model might improve the understanding of PD and may represent a promising tool to refine the evaluation of new therapeutic approaches

Gender effect on the Relation between Diabetes and Hospitalization for Heart Failure

Aims: Cardiovascular risk among diabetic patients is at least twice as much the one for nondiabetic individuals and even greater when diabetic women are considered. Heart failure (HF) is a common unfavorable outcome of cardiovascular disease in diabetes. However, since the comparison among sexes of heart failure prevalence in diabetic patients remains limited, this study is aimed at expanding the information about this point. Methods: We have evaluated the association between diabetes and HF by reviewing the medical records of all subjects discharged from the Internal Medicine and Cardiology Units of all hospitals in the Tuscany region, Italy, during the period January 2002 through December 2008. In particular we sought concomitance of ICD-9-CM codes for diabetes and HF. Results: Patients discharged by Internal Medicine were on average older, more represented by women, and had a lesser number of individuals coded as diabetic (p < 0.05 for all). Relative risk for HF (95 % CI) was signifi cantly higher in patients with diabetes, irrespective of gender 1.39 (1.36– 1.41) in males; 1.40 (1.37–1.42) in females. When the diabetes-HF association was analyzed according to decades of age, a “horse-shoe” pattern was apparent with an increased risk in 40–59 years old in female patients discharged by Internal Medicine. Conclusions: Although there is not a diff erence in the overall HF risk between hospitalized male and female diabetic patients, women have an excess risk at perimenopausal ag

Lactate, N-acetylaspartate, choline and creatine concentrations, and spin-spin relaxation in thalamic and occipito-parietal regions of developing human brain

Previous studies of the brains of normal infants demonstrated lower lactate (Lac)/choline (Cho), Lac/creatine (Cr), and Lac/ N-acetylaspartate (Naa) peak-area ratios in the thalamic region (predominantly gray matter) compared with occipitoparietal (mainly unmyelinated white matter) values. In the present study, thalamic Cho, Cr, and Naa concentrations between 32-42 weeks\u27 gestational plus postnatal age were greater than occipito-parietal: 4.6 +/- 0.8 (mean +/- SE), 10.5 +/- 2.0, and 9.0 +/- 0.7 versus 1.8 +/- 0.6, 5.8 +/- 1.5, and 3.4 +/- 1.1 mmol/kg wet weight, respectively: Lac concentrations were similar, 2.7 +/- 0.6 and 3.3 +/- 1.3 mmol/kg wet weight, respectively. In the thalamic region, Cho and Naa T2s increased, and Cho and Lac concentrations decreased, during development. Lower thalamic Lac peak-area ratios are principally due to higher thalamic concentrations of Cho, Cr, and Naa rather than less Lac. The high thalamic Cho concentration may relate to active myelination; the high thalamic Naa concentration may be due to advanced gray-matter development including active myelination. Lac concentration is higher in neonatal than in adult brain

The Lisbon patient: Exceptional longevity with HIV suggests healthy aging as an ultimate goal for HIV care

In the context of global aging, HIV infection has become a new chronic disease and requires innovative models of care. Treating isolated comorbidities represents a useless and potentially harmful practice at advanced age. Therefore, a patient-centered approach, in which the interventions are focused on the biology and function of the individual, with understanding of the importance of securing social and home environment that provides psychosocial support, better suits unmet health needs. We present a paradigmatic case of healthy aging: the first reported HIV-infected patient who achieved 100th of life - the Lisbon patient. The construct of healthy aging, recently introduced by the World Health Organization, is the best example of this comprehensive model and could represent the fourth target of UNAIDS agenda of the end of AIDS

Search for supersymmetry in final states with missing transverse momentum and three or more b-jets in 139 fb⁻¹ of proton–proton collisions at √s=13 TeV with the ATLAS detector

A search for supersymmetry involving the pair production of gluinos decaying via off-shell third-generation squarks into the lightest neutralino ( ˜χ01 ) is reported. It exploits LHC proton–proton collision data at a centre-of-mass energy √s = 13 TeV with an integrated luminosity of 139 fb−1 collected with the ATLAS detector from 2015 to 2018. The search uses events containing large missing transverse momentum, up to one electron or muon, and several energetic jets, at least three of which must be identified as containing b-hadrons. Both a simple kinematic event selection and an event selection based upon a deep neural-network are used. No significant excess above the predicted background is found. In simplified models involving the pair production of gluinos that decay via off-shell top (bottom) squarks, gluino masses less than 2.44 TeV (2.35 TeV) are excluded at 95% CL for a massless ˜χ01. Limits are also set on the gluino mass in models with variable branching ratios for gluino decays to b¯b˜χ01, t¯t˜χ01 and t¯b˜χ−1 /¯tb˜χ+1