The functioning of the mechanisms of constitutional control: some reflections on the basis of the european experience

The paper analyzes the evolution of the constitutional control from the beginning of the XIX century till nowadays. The basic model of constitutional control, its various functions, ways of forming and qualifying features of these legal institutions are reviewed. Author notes the special increasing role of the constitutional control of the European Court and the European Court of Human Rights. In this regard, author emphasizes the legal trend for reduce of the role of the constitutional control of some European countries in the protection of civil rights and a definite shift to their activity to the sphere of conflict resolution and the distribution of powers between the state authorities, in particular, between the central government and local authoritie

Cardiac magnetic resonance in heart failure with preserved ejection fraction:myocyte, interstitium, microvascular, and metabolic abnormalities

Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose prevalence continues to rise, with high social and economic burden, but with no specific approved treatment. Patients diagnosed with HFpEF have a high prevalence of comorbidities and exhibit a high misdiagnosis rate. True HFpEF is likely to have multiple pathophysiological causes - with these causes being clinically ill-defined due to limitations of current measurement techniques. Myocyte, interstitium, microvascular, and metabolic abnormalities have been regarded as key components of the pathophysiology and potential therapeutic targets. Cardiac magnetic resonance (CMR) has the capability to look deeper with a number of tissue characterization techniques which are closer to the underlying specific abnormalities and which could be linked to personalized medicine for HFpEF. This review aims to discuss the potential role of CMR to better define HFpEF phenotypes and to infer measurable therapeutic targets

Control system for ion Penning traps at the AEgIS experiment at CERN

The AEgIS experiment located at the Antiproton Decelerator at CERN aims to measure the gravitational fall of a cold antihydrogen pulsed beam. The precise observation of the antiatoms in the Earth gravitational field requires a controlled production and manipulation of antihydrogen. The neutral antimatter is obtained via a charge exchange reaction between a cold plasma of antiprotons from ELENA decelerator and a pulse of Rydberg positronium atoms. The current custom electronics designed to operate the 5 and 1 T Penning traps are going to be replaced by a control system based on the ARTIQ & Sinara open hardware and software ecosystem. This solution is present in many atomic, molecular and optical physics experiments and devices such as quantum computers. We report the status of the implementation as well as the main features of the new control system

High-resolution MCP-TimePix3 imaging/timing detector for antimatter physics

We present a hybrid imaging/timing detector for force sensitive inertial measurements designed for measurements on positronium, the metastable bound state of an electron and a positron, but also suitable for applications involving other low intensity, low energy beams of neutral (antimatter)-atoms, such as antihydrogen. The performance of the prototype detector was evaluated with a tunable low energy positron beam, resulting in a spatial resolution of approximate t

Development of a detector for inertial sensing of positronium at AEgIS (CERN)

The primary goal of the AEgIS collaboration at CERN is to measure the gravitational acceleration on neutral antimatter. Positronium (Ps), the bound state of an electron and a positron, is a suitable candidate for a force-sensitive inertial measurement by means of deflectometry/interferometry. In order to conduct such an experiment, the impact position and time of arrival of Ps atoms at the detector must be detected simultaneously. The detection of a low-velocity Ps beam with a spatial resolution of (88 ± 5) μm was previously demonstrated [1]. Based on the methodology employed in [1] and [2], a hybrid imaging/timing detector with increased spatial resolution of about 10 μm was developed. The performance of a prototype was tested with a positron beam. The concept of the detector and first results are presented

Positronium laser cooling via the 13S1^3S-23P2^3P transition with a broadband laser pulse

We report on laser cooling of a large fraction of positronium (Ps) in free-flight by strongly saturating the $1^3S$-$2^3P$ transition with a broadband, long-pulsed 243 nm alexandrite laser. The ground state Ps cloud is produced in a magnetic and electric field-free environment. We observe two different laser-induced effects. The first effect is an increase in the number of atoms in the ground state after the time Ps has spent in the long-lived $3^3P$ states. The second effect is the one-dimensional Doppler cooling of Ps, reducing the cloud's temperature from 380(20) K to 170(20) K. We demonstrate a 58(9) % increase in the coldest fraction of the Ps ensemble.Comment: 6 pages, 5 figure

Small interfering RNA targeting mcl-1 enhances proteasome inhibitor-induced apoptosis in various solid malignant tumors

<p>Abstract</p> <p>Background</p> <p>Targeting the ubiquitin-proteasome pathway is a promising approach for anticancer strategies. Recently, we found Bik accumulation in cancer cell lines after they were treated with bortezomib. However, recent evidence indicates that proteasome inhibitors may also induce the accumulation of anti-apoptotic Bcl-2 family members. The current study was designed to analyze the levels of several anti-apoptotic members of Bcl-2 family in different human cancer cell lines after they were treated with proteasome inhibitors.</p> <p>Methods</p> <p>Different human cancer cell lines were treated with proteasome inhibitors. Western blot were used to investigate the expression of Mcl-1 and activation of mitochondrial apoptotic signaling. Cell viability was investigated using SRB assay, and induction of apoptosis was measured using flow cytometry.</p> <p>Results</p> <p>We found elevated Mcl-1 level in human colon cancer cell lines DLD1, LOVO, SW620, and HCT116; human ovarian cancer cell line SKOV3; and human lung cancer cell line H1299, but not in human breast cancer cell line MCF7 after they were treated with bortezomib. This dramatic Mcl-1 accumulation was also observed when cells were treated with other two proteasome inhibitors, MG132 and calpain inhibitor I (ALLN). Moreover, our results showed Mcl-1 accumulation was caused by stabilization of the protein against degradation. Reducing Mcl-1 accumulation by Mcl-1 siRNA reduced Mcl-1 accumulation and enhanced proteasome inhibitor-induced cell death and apoptosis, as evidenced by the increased cleavage of caspase-9, caspase-3, and poly (ADP-ribose) polymerase.</p> <p>Conclusions</p> <p>Our results showed that it was not only Bik but also Mcl-1 accumulation during the treatment of proteasome inhibitors, and combining proteasome inhibitors with Mcl-1 siRNA would enhance the ultimate anticancer effect suggesting this combination might be a more effective strategy for cancer therapy.</p

A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation &amp; Right Ventricular Function

\ua9 2024 The Authors. European Journal of Heart Failure published by John Wiley &amp; Sons Ltd on behalf of European Society of Cardiology.Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF

Feasibility studies for imaging e+^{+}e−^{-} annihilation with modular multi-strip detectors

Studies based on imaging the annihilation of the electron (e$^{-}$) and its antiparticle positron (e$^{+}$) open up several interesting applications in nuclear medicine and fundamental research. The annihilation process involves both the direct conversion of e$^{+}$e$^{-}$ into photons and the formation of their atomically bound state, the positronium atom (Ps), which can be used as a probe for fundamental studies. With the ability to produce large quantities of Ps, manipulate them in long-lived Ps states, and image their annihilations after a free fall or after passing through atomic interferometers, this purely leptonic antimatter system can be used to perform inertial sensing studies in view of a direct test of Einstein equivalence principle. It is envisioned that modular multistrip detectors can be exploited as potential detection units for this kind of studies. In this work, we report the results of the first feasibility study performed on a e$^{+}$ beamline using two detection modules to evaluate their reconstruction performance and spatial resolution for imaging e$^{+}$e$^{-}$ annihilations and thus their applicability for gravitational studies of Ps