Discovering gravitational lenses with artificial intelligence

Gravitational lensing is a phenomenon that occurs when the light from a background galaxy is bent by a foreground galaxy before reaching the observer.Gravitational lenses are a unique tool to study the structure of galaxies and to measure fundamental cosmological parameters such as the expansion rate of the Universe.Thus, it is important to identify these occurences of aligned galaxies which are particularly rare, about one for each thousand galaxies.Traditionally, this search has heavily relied on the visual inspection of images by astronomers.However, it has becoming increasingly difficult to build complete samples of gravitational lenses in such a way because upcoming astronomical surveys are going to observe billions of galaxies. For this reason it is essential to develop automatic lens-finder algorithms.In this thesis, I have developed and trained machine learning algorithms based on artificial neural networks to identify gravitational lenses in the Kilo-Degree Survey (KiDS). KiDS is an optical survey that has observed part of the South sky with unprecedented image quality.The artificial neural networks have analyzed images of tens of thousands galaxies and have aided in discovering hundreds of new gravitational lens candidates for which the images are being collected at the website https://www.astro.rug.nl/lensesinkids.This way I have demonstrated that applying these kinds of automatic methods for finding gravitational lenses is feasible in large sets of imaging data. In fact, many millions of galaxies will be analyzed by a computer neural network instead of a human eye and its neural network. This way it will be possible to select thousands of lens candidates as input for astrophysical research with minimal human intervention

Oxidative stress in DNA repeat expansion disorders: a focus on NRF2 signaling involvement

DNA repeat expansion disorders are a group of neuromuscular and neurodegenerative diseases that arise from the inheritance of long tracts of nucleotide repetitions, located in the regulatory region, introns, or inside the coding sequence of a gene. Although loss of protein expression and/or the gain of function of its transcribed mRNA or translated product represent the major pathogenic effect of these pathologies, mitochondrial dysfunction and imbalance in redox homeostasis are reported as common features in these disorders, deeply affecting their severity and progression. In this review, we examine the role that the redox imbalance plays in the pathological mechanisms of DNA expansion disorders and the recent advances on antioxidant treatments, particularly focusing on the expression and the activity of the transcription factor NRF2, the main cellular regulator of the antioxidant response

Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway

Oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD), an X-linked genetic disorder caused by mutations in the dystrophin gene and characterized by progressive, lethal muscle degeneration and chronic inflammation. In this study, we explored the expression and signaling pathway of a master player of the anti-oxidant and anti-inflammatory response, namely NRF2, in muscle biopsies of DMD patients. We classified DMD patients in two age groups (Class I, 0-2 years and Class II, 2-9 years), in order to evaluate the antioxidant pathway expression during the disease progression. We observed that altered enzymatic antioxidant responses, increased levels of oxidized glutathione and oxidative damage are differently modulated in the two age classes of patients and well correlate with the severity of pathology. Interestingly, we also observed a modulation of relevant markers of the inflammatory response, such as heme oxygenase 1 and IL-6, suggesting a link between oxidative stress and chronic inflammatory response. Of note, using a transgenic mouse model, we demonstrated that IL-6 overexpression parallels the antioxidant expression profile and the severity of dystrophic muscle observed in DMD patients. This study advances our understanding of the pathogenic mechanisms underlying DMD and defines the critical role of oxidative stress on muscle wasting with clear implications for disease pathogenesis and therapy in human

Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway

Oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD), an X-linked genetic disorder caused by mutations in the dystrophin gene and characterized by progressive, lethal muscle degeneration and chronic inflammation. In this study, we explored the expression and signaling pathway of a master player of the anti-oxidant and anti-inflammatory response, namely NRF2, in muscle biopsies of DMD patients. We classified DMD patients in two age groups (Class I, 0-2 years and Class II, 2-9 years), in order to evaluate the antioxidant pathway expression during the disease progression. We observed that altered enzymatic antioxidant responses, increased levels of oxidized glutathione and oxidative damage are differently modulated in the two age classes of patients and well correlate with the severity of pathology. Interestingly, we also observed a modulation of relevant markers of the inflammatory response, such as heme oxygenase 1 and IL-6, suggesting a link between oxidative stress and chronic inflammatory response. Of note, using a transgenic mouse model, we demonstrated that IL-6 overexpression parallels the antioxidant expression profile and the severity of dystrophic muscle observed in DMD patients. This study advances our understanding of the pathogenic mechanisms underlying DMD and defines the critical role of oxidative stress on muscle wasting with clear implications for disease pathogenesis and therapy in human

Targeting NRF2 for the treatment of Friedreich's ataxia: a comparison among drugs

NRF2 (Nuclear factor Erythroid 2-related Factor 2) signaling is impaired in Friedreich's Ataxia (FRDA), an autosomal recessive disease characterized by progressive nervous system damage and degeneration of nerve fibers in the spinal cord and peripheral nerves. The loss of frataxin in patients results in iron sulfur cluster deficiency and iron accumulation in the mitochondria, making FRDA a fatal and debilitating condition. There are no currently approved therapies for the treatment of FRDA and molecules able to activate NRF2 have the potential to induce clinical benefits in patients. In this study, we compared the efficacy of six redox-active drugs, some already adopted in clinical trials, targeting NRF2 activation and frataxin expression in fibroblasts obtained from skin biopsies of FRDA patients. All of these drugs consistently increased NRF2 expression, but differential profiles of NRF2 downstream genes were activated. The Sulforaphane and N-acetylcysteine were particularly effective on genes involved in preventing inflammation and maintaining glutathione homeostasis, the dimethyl fumarate, omaxevolone, and EPI-743 in counteracting toxic products accumulation, the idebenone in mitochondrial protection. This study may contribute to develop synergic therapies, based on a combination of treatment molecules

Ferroptosis in Friedreich’s ataxia: a metal-induced neurodegenerative disease

Ferroptosis is an iron-dependent form of regulated cell death, arising from the accumulation of lipid-based reactive oxygen species when glutathione-dependent repair systems are compromised. Lipid peroxidation, mitochondrial impairment and iron dyshomeostasis are the hallmark of ferroptosis, which is emerging as a crucial player in neurodegeneration. This review provides an analysis of the most recent advances in ferroptosis, with a special focus on Friedreich’s Ataxia (FA), the most common autosomal recessive neurodegenerative disease, caused by reduced levels of frataxin, a mitochondrial protein involved in iron–sulfur cluster synthesis and antioxidant defenses. The hypothesis is that the iron-induced oxidative damage accumulates over time in FA, lowering the ferroptosis threshold and leading to neuronal cell death and, at last, to cardiac failure. The use of anti-ferroptosis drugs combined with treatments able to activate the antioxidant response will be of paramount importance in FA therapy, such as in many other neurodegenerative diseases triggered by oxidative stress

Compact object coalescence rate estimation from short gamma-ray burst observations

Recent observational and theoretical results suggest that Short-duration Gamma-Ray Bursts (SGRBs) are originated by the merger of compact binary systems of two neutron stars or a neutron star and a black hole. The observation of SGRBs with known redshifts allows astronomers to infer the merger rate of these systems in the local universe. We use data from the SWIFT satellite to estimate this rate to be in the range $\sim 500$-1500 Gpc$^{-3}$yr$^{-1}$. This result is consistent with earlier published results which were obtained through alternative approaches. We estimate the number of coincident observations of gravitational-wave signals with SGRBs in the advanced gravitational-wave detector era. By assuming that all SGRBs are created by neutron star-neutron star (neutron star-black hole) mergers, we estimate the expected rate of coincident observations to be in the range $\simeq 0.2$ to 1 ($\simeq 1$ to 3) yr$^{-1}$.Comment: 23 pages, 3 figures, version accepted for publicatio

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of numerous drugs with an increasingly significant role in clinical therapy especially of cancer patients. Here, we provide an overview of clinical epigenetics within the context of network analysis. We illustrate achievements to date and discuss how we can move from traditional medicine into the era of network medicine (NM), where pathway-informed molecular diagnostics will allow treatment selection following the paradigm of precision medicine

Mechanistic and phenotypic studies of bicarinalin, BP100 and colistin action on Acinetobacter baumannii

Acinetobacter baumannii has been identified by the WHO as a high priority pathogen. It can be resistant to multiple antibiotics and colistin sulphate is often used as a last-resort treatment. However, the potentially severe side-effects of colistin are well documented and this study compared the bactericidal and anti-biofilm activity of two synthetic nature-inspired antimicrobial peptides, bicarinalin and BP100, with colistin. The minimum bactericidal concentration (MBC) against planktonic A. baumannii was approximately 0.5 μg/ml for colistin sulphate and ∼4 μg/ml for bicarinalin and BP100. A. baumannii commonly occurs as a biofilm and biofilm removal assay results highlighted that both bicarinalin and BP100 had significantly greater potential than colistin. Atomic force microscopy (AFM) showed dramatic changes in A. baumannii cell size and surface conformity when treated with peptide concentrations at and above the MBC. Scanning electron microscopy (SEM) visualised the reduction of biofilm coverage and cell surface changes as peptide concentration increased. Liposome assays revealed that these peptides most likely act as pore-forming agents in the membrane. Bicarinalin and BP100 may be effective therapeutic alternatives to colistin against A. baumannii infections but further research is required to assess if they elicit cytotoxicity issues in patients

Building the largest spectroscopic sample of ultra-compact massive galaxies with the Kilo Degree Survey

Ultra-compact massive galaxies UCMGs, i.e. galaxies with stellar masses $M_{*} > 8 \times 10^{10} M_{\odot}$ and effective radii $R_{e} < 1.5$ kpc, are very rare systems, in particular at low and intermediate redshifts. Their origin as well as their number density across cosmic time are still under scrutiny, especially because of the paucity of spectroscopically confirmed samples. We have started a systematic census of UCMG candidates within the ESO Kilo Degree Survey, together with a large spectroscopic follow-up campaign to build the largest possible sample of confirmed UCMGs. This is the third paper of the series and the second based on the spectroscopic follow-up program. Here, we present photometrical and structural parameters of 33 new candidates at redshifts $0.15 \lesssim z \lesssim 0.5$ and confirm 19 of them as UCMGs, based on their nominal spectroscopically inferred $M_{*}$ and $R_{e}$. This corresponds to a success rate of $\sim 58\%$, nicely consistent with our previous findings. The addition of these 19 newly confirmed objects, allows us to fully assess the systematics on the system selection, and finally reduce the number density uncertainties. Moreover, putting together the results from our current and past observational campaigns and some literature data, we build the largest sample of UCMGs ever collected, comprising 92 spectroscopically confirmed objects at $0.1 \lesssim z \lesssim 0.5$. This number raises to 116, allowing for a $3\sigma$ tolerance on the $M_{*}$ and $R_{e}$ thresholds for the UCMG definition. For all these galaxies we have estimated the velocity dispersion values at the effective radii which have been used to derive a preliminary mass-velocity dispersion correlation