Publications by authors named "Leber R"

A bread wheat panel reveals rich genetic diversity in Turkish, Pakistani and Iranian landraces and novel resistance loci to diverse powdery mildew isolates via subsetting approaches in association studies. Wheat breeding for disease resistance relies on the availability and use of diverse genetic resources. More than 800,000 wheat accessions are globally conserved in gene banks, but they are mostly uncharacterized for the presence of resistance genes and their potential for agriculture.

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We previously reported that the synergistically enhanced antimicrobial activity of magainin 2 (MG2a) and PGLa is related to membrane adhesion and fusion. Here, we demonstrate that equimolar mixtures of MG2a and L18W-PGLa induce positive monolayer curvature stress and sense, at the same time, positive mean and Gaussian bilayer curvatures already at low amounts of bound peptide. The combination of both abilities-membrane curvature sensing and inducing-is most likely the base for the synergistically enhanced peptide activity.

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Background: The healthcare burden posed by the coronavirus disease 2019 (COVID-19) pandemic in the New York Metropolitan area has necessitated the postponement of elective procedures resulting in a marked reduction in cardiac catheterization laboratory (CCL) volumes with a potential to impact interventional cardiology (IC) fellowship training.

Methods: We conducted a web-based survey sent electronically to 21 Accreditation Council for Graduate Medical Education accredited IC fellowship program directors (PDs) and their respective fellows.

Results: Fourteen programs (67%) responded to the survey and all acknowledged a significant decrease in CCL procedural volumes.

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The aim of this study was to develop effective and specific anti-cancer drugs based on membrane active peptides. In previous studies we showed that human lactoferricin (hLFcin) derived peptides facilitate specific killing of cancer cells. These antitumor peptides were found by conventional melanoma two-dimensional (2D) cell cultures to induce apoptosis of cancer cells and to specifically target lipid phosphatidylserine located on the outside of cancer cell membranes.

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The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, β-fold structure rendering them highly stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo. The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins.

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Aim: Exercise stress testing is used to detect myocardial ischaemia, but is limited by low sensitivity and specificity. The authors investigated the value of the analysis of high-frequency QRS components as a marker of abnormal depolarization in addition to standard ST-deviations as a marker of abnormal repolarization to improve the diagnostic accuracy.

Methods And Results: Consecutive patients undergoing bicycle exercise stress nuclear myocardial perfusion imaging were prospectively enrolled.

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Article Synopsis
  • R-DIM-P-LF11-322 and DIM-LF11-318 are peptides derived from lactoferricin that show anti-tumor effects on human melanoma, but R-DIM-P-LF11-322 targets cancer cells specifically, while DIM-LF11-318 acts on both cancer and healthy cells.
  • Research indicates that cancer cells expose negatively charged phosphatidylserine (PS) on their surface, which R-DIM-P-LF11-322 binds to, whereas cholesterol can diminish its effectiveness.
  • In contrast, DIM-LF11-318 interacts with PS and other lipids without being influenced by cholesterol, and while R-DIM-P-LF11-322 enters the cancer cells and induces
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Background: Automated measurements of electrocardiographic (ECG) intervals by current-generation digital electrocardiographs are critical to computer-based ECG diagnostic statements, to serial comparison of ECGs, and to epidemiological studies of ECG findings in populations. A previous study demonstrated generally small but often significant systematic differences among 4 algorithms widely used for automated ECG in the United States and that measurement differences could be related to the degree of abnormality of the underlying tracing. Since that publication, some algorithms have been adjusted, whereas other large manufacturers of automated ECGs have asked to participate in an extension of this comparison.

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Mixtures of the frog peptides magainin 2 and PGLa are well-known for their pronounced synergistic killing of Gram-negative bacteria. We aimed to gain insight into the underlying biophysical mechanism by interrogating the permeabilizing efficacies of the peptides as a function of stored membrane curvature strain. For Gram-negative bacterial-inner-membrane mimics, synergism was only observed when the anionic bilayers exhibited significant negative intrinsic curvatures imposed by monounsaturated phosphatidylethanolamine.

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Background: Exercise ECG stress testing is the most widely available method for evaluation of patients with suspected myocardial ischemia. Its major limitation is the relatively poor accuracy of ST-segment changes regarding ischemia detection. Little is known about the optimal method to assess ST-deviations.

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Background: The V-index is an ECG marker quantifying spatial heterogeneity of ventricular repolarization. We prospectively assessed the diagnostic and prognostic values of the V-index in patients with suspected non-ST-elevation myocardial infarction (NSTEMI).

Methods: We prospectively enrolled 497 patients presenting with suspected NSTEMI to the emergency department (ED).

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We aimed to assess the diagnostic and prognostic value of ST-segment deviation in aVR, a lead often ignored in clinical practice, during exercise testing and to compare it to the most widely used criterion of ST-segment depression in V. We enrolled 1,596 patients with suspected myocardial ischemia referred for nuclear perfusion imaging undergoing bicycle stress testing. ST-segment amplitudes in leads aVR and V were automatically measured.

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Background And Objective: The first-order high-pass filter (AC coupling) has previously been shown to affect the ECG for higher cut-off frequencies. We seek to find a systematic deviation in computer measurements of the electrocardiogram when the AC coupling with a 0.05 Hz first-order high-pass filter is used.

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Goal: The ST segment of an electrocardiogram (ECG) is very important for the correct diagnosis of an acute myocardial infarction. Most clinical ECGs are recorded using an ACcoupled ECG amplifier. It is well known, that first-order high-pass filters used for the AC coupling can affect the ST segment of an ECG.

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Background: Electrocardiogram (ECG) biometrics is an advanced technology, not yet covered by guidelines on criteria, features and leads for maximal authentication accuracy.

Objective: This study aims to define the minimal set of morphological metrics in 12-lead ECG by optimization towards high reliability and security, and validation in a person verification model across a large population.

Methods: A standard 12-lead resting ECG database from 574 non-cardiac patients with two remote recordings (>1year apart) was used.

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Background And Objective: A crucial factor for proper electrocardiogram (ECG) interpretation is the correct electrode placement in standard 12-lead ECG and extended 16-lead ECG for accurate diagnosis of acute myocardial infarctions. In the context of optimal patient care, we present and evaluate a new method for automated detection of reversals in peripheral and precordial (standard, right and posterior) leads, based on simple rules with inter-lead correlation dependencies.

Methods: The algorithm for analysis of cable reversals relies on scoring of inter-lead correlations estimated over 4s snapshots with time-coherent data from multiple ECG leads.

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False intensive care unit (ICU) alarms induce stress in both patients and clinical staff and decrease the quality of care, thus significantly increasing both the hospital recovery time and rehospitalization rates. In the PhysioNet/CinC Challenge 2015 for reducing false arrhythmia alarms in ICU bedside monitor data, this paper validates the application of a real-time arrhythmia detection library (ADLib, Schiller AG) for the robust detection of five types of life-threatening arrhythmia alarms. The strength of the application is to give immediate feedback on the arrhythmia event within a scan interval of 3 s-7.

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Arrhythmogenic cardiomyopathy (ACM) is characterized by redistribution of junctional proteins, arrhythmias, and progressive myocardial injury. We previously reported that SB216763 (SB2), annotated as a GSK3β inhibitor, reverses disease phenotypes in a zebrafish model of ACM. Here, we show that SB2 prevents myocyte injury and cardiac dysfunction in vivo in two murine models of ACM at baseline and in response to exercise.

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Since the introduction of digital electrocardiographs, high-pass filters have been necessary for successful analog-to-digital conversion with a reasonable amplitude resolution. On the other hand, such high-pass filters may distort the diagnostically significant ST-segment of the ECG, which can result in a misleading diagnosis. We present an inverting filter that successfully undoes the effects of a 0.

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This study presents a 2-stage heartbeat classifier of supraventricular (SVB) and ventricular (VB) beats. Stage 1 makes computationally-efficient classification of SVB-beats, using simple correlation threshold criterion for finding close match with a predominant normal (reference) beat template. The non-matched beats are next subjected to measurement of 20 basic features, tracking the beat and reference template morphology and RR-variability for subsequent refined classification in SVB or VB-class by Stage 2.

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Host defense-derived peptides have emerged as a novel strategy for the development of alternative anticancer therapies. In this study we report on characteristic features of human lactoferricin (hLFcin) derivatives which facilitate specific killing of cancer cells of melanoma, glioblastoma and rhabdomyosarcoma compared with non-specific derivatives and the synthetic peptide RW-AH. Changes in amino acid sequence of hLFcin providing 9-11 amino acids stretched derivatives LF11-316, -318 and -322 only yielded low antitumor activity.

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OP-145, a synthetic antimicrobial peptide developed from a screen of the human cathelicidin LL-37, displays strong antibacterial activities and is--at considerably higher concentrations--lytic to human cells. To obtain more insight into its actions, we investigated the interactions between OP-145 and liposomes composed of phosphatidylglycerol (PG) and phosphatidylcholine (PC), resembling bacterial and mammalian membranes, respectively. Circular dichroism analyses of OP-145 demonstrated a predominant α-helical conformation in the presence of both membrane mimics, indicating that the different membrane-perturbation mechanisms are not due to different secondary structures.

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The objective of this study was to evaluate the impact of nebulization on liposomes with specific surface characteristics by applying three commercially available inhaler systems (air-jet, ultrasonic and vibrating-mesh). Conventional liposome formulations composed of phosphatidylcholine and cholesterol were compared to sterically stabilized PEGylated liposomes and cationic polymer coated liposomes.Liposomes of similar size (between 140 and 165 nm in diameter with polydispersity indices <0.

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Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud's phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems.

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Aim: We investigated the feasibility and safety of intra-arterial bivalirudin bolus during primary angioplasty.

Background: Bivalirudin has been shown to be an effective and safe anticoagulant during angioplasty. However, in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial, the bivalirudin group experienced higher acute stent thrombosis rate compared with the heparin and glycoprotein IIb/IIIa inhibitor group.

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