Reality property of discrete Wronski map with imaginary step

For a set of quasi-exponentials with real exponents, we consider the discrete Wronskian (also known as Casorati determinant) with pure imaginary step 2h. We prove that if the coefficients of the discrete Wronskian are real and for every its roots the imaginary part is at most |h|, then the complex span of this set of quasi-exponentials has a basis consisting of quasi-exponentials with real coefficients. This result is a generalization of the statement of the B. and M. Shapiro conjecture on spaces of polynomials. The proof is based on the Bethe ansatz for the XXX model.Comment: Latex, 9 page

Short-Term Therapies for Treatment of Acute and Advanced Heart Failure—Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline?

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio- and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g., catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents

Short-Term Therapies for Treatment of Acute and Advanced Heart Failure—Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline?

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio- and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g., catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years

<i>In silico</i> analysis of genomes of Bacillus anthracis strains belonging to major genetic lineages

Introduction. The global phylogenetic population structure of Bacillus anthracis is represented by major genetic lineages (A, B and C) with nonuniform distribution of isolates, which still cannot be explained. Identification of characteristics of genomes of strains from three lineages, which can affect their spread, is of high importance. The aim of the study is to explore genomic characteristics of different genetic lineages, which may have an effect on their distribution, by using the in silico analysis of a representative subset of B. anthracis strains. Materials and methods. The whole-genome sequences of 49 B. anthracis strains and Bacillus cereus biovar anthracis CI strain were studied. The in silico analysis was performed to identify polymorphisms using BLASTn, MEGA X, Tandem Repeat Finder, Parsnp the Harvest Suite software. Results. The genome variability depended on single nucleotide polymorphisms, single-nucleotide repeats, number of tandem repeats, substitutions and indels. In strains from lineages B and C, they outnumbered 1.613.4 times and in the B. cereus biovar anthracis strain 5150 times those in B. anthracis strains from lineage A. Significant substitutions in housekeeping genes and pathogenicity factor genes caused changes in amino acid sequences in proteins significantly more frequently in B. anthracis strains from major lineages B and C. Based on the molecular typing and a multi-virulence-locus sequence typing analysis (MVLST) with a discrimination index of 0.9633, strains were classified into three major genetic lineages including groups different from the canonical group. Conclusion. The distinctive feature of B. anthracis genomes is that they have a larger number of significant nucleotide substitutions in pathogenicity factor genes and housekeeping genes of strains belonging to major lineages B and C compared to lineage A. Changes in proteins encoded by them can cause differences in ecological adaptation and in prevalence, which are higher in strains of lineage A. MVLST having a high discriminating capacity can be used as an additional method to B. anthracis molecular typing

Mapping Magnetic Properties and Relaxation in Vanadium(IV) Complexes with Lanthanides by Electron Paramagnetic Resonance

Vanadium(IV) complexes are actively studied as potential candidates for molecular spin qubits operating at room temperatures. They have longer electron spin decoherence times than many other transition ions, being the key property for applications in quantum information processing. In most cases reported to date, the molecular complexes were optimized through the design for this purpose. In this work, we investigate the relaxation properties of vanadium(IV) ions incorporated in complexes with lanthanides using electron paramagnetic resonance (EPR). In all cases, the VO6 moieties with no nuclear spins in the first coordination sphere are addressed. We develop and implement the approaches for facile diagnostics of relaxation characteristics in individual VO6 moieties of such compounds. Remarkably, the estimated relaxation times are found to be close to those of other vanadium-based qubits obtained previously. In the future, a synergistic combination of qubit-friendly properties of vanadium ions with single-molecule magnetism and luminescence of lanthanides can be pursued to realize new functionalities of such materials

Electrostatic Origin of Stabilization in MoS₂–Organic Nanocrystals

Negatively charged molybdenum disulfide layers form stable organic–inorganic layered nanocrystals when reacted with organic cations in solution. The reasons why this self-assembly process leads to a single-phase compound with a well-defined interlayer distance in given conditions are, however, poorly understood to date. Here, for the first time, we quantify the interactions determining the cation packing and stability of the MoS₂–organic nanocrystals and find that the main contribution arises from Coulomb forces. The study was performed on the series of new layered compounds of MoS₂ with naphthalene derivatives, forming several distinct phases depending on reaction conditions. Starting with structural models derived from powder X-ray diffraction data and TEM, we evaluate their cohesion energy by modeling layer separation with periodic PW-DFT-D calculations. The results provide a reliable approach for estimation of the stability of MoS₂-based heterolayered compounds

Electrostatic Origin of Stabilization in MoS₂–Organic Nanocrystals

Negatively charged molybdenum disulfide layers form stable organic–inorganic layered nanocrystals when reacted with organic cations in solution. The reasons why this self-assembly process leads to a single-phase compound with a well-defined interlayer distance in given conditions are, however, poorly understood to date. Here, for the first time, we quantify the interactions determining the cation packing and stability of the MoS₂–organic nanocrystals and find that the main contribution arises from Coulomb forces. The study was performed on the series of new layered compounds of MoS₂ with naphthalene derivatives, forming several distinct phases depending on reaction conditions. Starting with structural models derived from powder X-ray diffraction data and TEM, we evaluate their cohesion energy by modeling layer separation with periodic PW-DFT-D calculations. The results provide a reliable approach for estimation of the stability of MoS₂-based heterolayered compounds