High-Statistics Measurement of the Cosmic-Ray Electron Spectrum with H.E.S.S.

Owing to their rapid cooling rate and hence loss-limited propagation distance, cosmic-ray electrons and positrons (CRe) at very high energies probe local cosmic-ray accelerators and provide constraints on exotic production mechanisms such as annihilation of dark matter particles. We present a high-statistics measurement of the spectrum of CRe candidate events from 0.3 to 40 TeV with the High Energy Stereoscopic System, covering 2 orders of magnitude in energy and reaching a proton rejection power of better than 10^{4}.

Acceleration and transport of relativistic electrons in the jets of the microquasar SS 433.

SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.

Search for Dark Matter Annihilation Signals in the H.E.S.S. Inner Galaxy Survey.

The central region of the Milky Way is one of the foremost locations to look for dark matter (DM) signatures. We report the first results on a search for DM particle annihilation signals using new observations from an unprecedented γ-ray survey of the Galactic Center (GC) region, i.e.

Time-resolved hadronic particle acceleration in the recurrent nova RS Ophiuchi.

Recurrent novae are repeating thermonuclear explosions in the outer layers of white dwarfs, due to the accretion of fresh material from a binary companion. The shock generated when ejected material slams into the companion star's wind can accelerate particles. We report very-high-energy (VHE; [Formula: see text]) gamma rays from the recurrent nova RS Ophiuchi, up to 1 month after its 2021 outburst, observed using the High Energy Stereoscopic System (H.

Pulsed Field Ablation Versus Radiofrequency Ablation: Esophageal Injury in a Novel Porcine Model.

Background: Pulsed field ablation (PFA) can be myocardium selective, potentially sparing the esophagus during left atrial ablation. In an in vivo porcine esophageal injury model, we compared the effects of newer biphasic PFA with radiofrequency ablation (RFA).

Methods: In 10 animals, under general anesthesia, the lower esophagus was deflected toward the inferior vena cava using an esophageal deviation balloon, and ablation was performed from within the inferior vena cava at areas of esophageal contact.

Endocardial ventricular pulsed field ablation: a proof-of-concept preclinical evaluation.

Aims: Pulsed field ablation (PFA) is a novel, non-thermal modality that selectively ablates myocardium with ultra-short electrical impulses while sparing collateral tissues. In a proof-of-concept study, the safety and feasibility of ventricular PFA were assessed using a prototype steerable, endocardial catheter.

Methods And Results: Under general anaesthesia, the left and right ventricles of four healthy swine were ablated using the 12-Fr deflectable PFA catheter and a deflectable sheath guided by electroanatomic mapping.

Preclinical Evaluation of Pulsed Field Ablation: Electrophysiological and Histological Assessment of Thoracic Vein Isolation.

Background: Pulsed field ablation (PFA) is a uniquely tissue-selective, nonthermal cardiac ablation modality. Delivery parameters such as the electrical waveform composition and device design are critical to PFA's efficacy and safety, particularly tissue specificity. In a series of preclinical studies, we sought to examine the electrophysiological and histological effects of PFA and compare the safety and feasibility of durable pulmonary vein and superior vena cava (SVC) isolation between radiofrequency ablation and PFA waveforms.

Hydroxyurea Improves Spatial Memory and Cognitive Plasticity in Mice and Has a Mild Effect on These Parameters in a Down Syndrome Mouse Model.

Down syndrome (DS), a genetic disorder caused by partial or complete triplication of chromosome 21, is the most common genetic cause of intellectual disability. DS mouse models and cell lines display defects in cellular adaptive stress responses including autophagy, unfolded protein response, and mitochondrial bioenergetics. We tested the ability of hydroxyurea (HU), an FDA-approved pharmacological agent that activates adaptive cellular stress response pathways, to improve the cognitive function of Ts65Dn mice.

Hydroxyurea attenuates oxidative, metabolic, and excitotoxic stress in rat hippocampal neurons and improves spatial memory in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by accumulation of amyloid β-peptide (Aβ) plaques in the brain and decreased cognitive function leading to dementia. We tested if hydroxyurea (HU), a ribonucleotide reductase inhibitor known to activate adaptive cellular stress responses and ameliorate abnormalities associated with several genetic disorders, could protect rat hippocampal neurons against oxidative-, excitatory-, mitochondrial-, and Aβ-induced stress and if HU treatment could improve learning and memory in the APP/PS1 mouse model of AD. HU treatment attenuated the loss of cell viability induced by treatment of hippocampal neurons with hydrogen peroxide, glutamate, rotenone, and Aβ.

Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons.

Mitochondria are essential organelles whose biogenesis, structure, and function are regulated by many signaling pathways. We present evidence that, in hippocampal neurons, activation of the Sonic hedgehog (Shh) signaling pathway affects multiple aspects of mitochondria. Mitochondrial mass was increased significantly in neurons treated with Shh.

Activation of the stress proteome as a mechanism for small molecule therapeutics.

Various small molecule pharmacologic agents with different known functions produce similar outcomes in diverse Mendelian and complex disorders, suggesting that they may induce common cellular effects. These molecules include histone deacetylase inhibitors, 4-phenylbutyrate (4PBA) and trichostatin A, and two small molecules without direct histone deacetylase inhibitor activity, hydroxyurea (HU) and sulforaphane. In some cases, the therapeutic effects of histone deacetylase inhibitors have been attributed to an increase in expression of genes related to the disease-causing gene.

SOD2 as a potential modifier of X-linked adrenoleukodystrophy clinical phenotypes.

X-linked adrenoleukodystrophy (XALD), a neurological disorder caused by mutations in the peroxisomal membrane protein gene ABCD1, presents as a rapidly progressing, inflammatory cerebral demyelination (cerebral cases) or a slowly progressing, distal axonopathy (non-cerebral cases). Specific ABCD1 defects do not explain this significant phenotypic variation. Patients have increased plasma and tissue very long chain fatty acid levels and increased cellular oxidative stress and oxidative damage.

Alterations in the visual cortex receptor pattern by operant conditioning in a reward paradigm.

The aim of the study was to investigate the impact of operant conditioning on the receptor pattern in the visual cortex of calves. A reward paradigm was used to induce conditioned preference for colours. Binding sites in visual cortex specimens from conditioned and naive animals were assayed in vitro on cellular basis after dissociation of the tissue by collagenase, incubation with fluorescent ligands and flow-cytometry for fluorescence analysis.