Topological Order in the Phase Diagram for High-Temperature Superconductors with Point Defects

Applying a Lindemann-like criterion obtained previously by Kierfeld, Nattermann and Hwa [Phys. Rev. B 55, 626 (1997)], we estimate the magnetic field and temperature for a high-$T_c$ superconductor, at which a topologically ordered vortex glass phase becomes unstable with respect to a disorder-induced formation of dislocations. The employed criterion is shown to be equivalent to a conventional phenomenological Lindemann criterion including the values for the numerical factors, i.e., for the Lindemann-number. The positional correlation length of the topologically ordered vortex glass is calculated.Comment: 8 pages, REVTEX 3.0, uses epsf, 1 eps-figure, major changes: Lindemann-like criterion is applied to YBCO, the electromagnetic coupling and the possibility of strong pinning are considered, version accepted for publication in Physica

Notacijska analiza i frekvencija srca vrhunskih rukometašica (u19) zabilježena tijekom natjecateljskih utakmica

Heart rate and time-motion were examined in elite female handball players (U19) during six competitive matches. The average age of the participants was 17.9±0.3 years, the average mass was 65.4±6.9 kg, and the average height was 169.6±6.9 cm. Time-motion analyses of the players were performed using Video Manual Motion Tracker 1.0 software. The descriptive approach of the study determined the overall physical activity (distance [m]) and type of locomotion (standing, walking, jogging, medium-intensity running, high-intensity running, sprinting). The players’ heart rates were monitored using TEAM Polar2Pro sport testers (Polar Electro, Kempele, Finland). The maximum heart rate was measured by means of the Yo-Yo intermittent level 1 (YYIRT1) recovery test. One-way ANOVA with repeated-measures was used to compare data on heart rate, covered distance and speed. Based on the results from the time-motion analysis, the average distance covered was 113.3±8.6 m per minute per match. The average distance the players covered during the matches was 3399±362.3 m. The shortest distance (385.8±371.6 m), was traversed by standing and walking, and the longest distance (935.8±165.5 m) by jogging. The players’ average heart rate was 183.7±7.3 beats∙min-1. The mean intensity during the matches represented 89.6±3.6% of the maximal heart rate (HRmax). The results of this study demonstrate that handball is a high- intensity intermittent sport. The physiological profile shows that the players spent more than 83% of the playing time per match in the high-intensity zone (>85%HRmax). Based on this, training focused on anaerobic exercises and interval training methods is recommended. Anaerobic training ensures that players will be ready to carry out a high intensity performance and to maintain it during the whole match. Maintaining high intensity depends chiefly on the ability to replenish energy systems during the period spent in lower-intensity locomotion. We recommend improvements in anaerobic and aerobic power during practice sessions.U ovom istraživanju provedena je notacijska analiza te je zabilježena frekvencija srca vrhunskih rukometašica (U19) tijekom šest natjecateljskih utakmica. Prosječna dob ispitanica bila je 17,9±0,3 godina, tjelesna masa 65,4±6,9 kg, a prosječna tjelesna visina 169,6±6,9 cm. Notacijska analiza igračica provedena je pomoću Video Manual Motion Tracker 1.0 software. Opisana je ukupna tjelesna aktivnost tijekom utakmica (prijeđena udaljenost [m]) kao i kategorija kretanja (stajanje, hodanje, kaskanje, umjereno trčanje, visokointenzivno trčanje, sprint). Frekvencija srca praćena je sustavom TEAM Polar2Pro (Polar Electro, Kempele, Finska). Maksimalna frekvencija srca utvrđena je pomoću jo-jo testa (Yo Yo Intermittent Recovery Test). Jednostruka analiza varijance za ponovljena mjerenja je korištena za uspoređivanje rezultata frekvencije srca, prijeđene udaljenosti i brzine kretanja. Na temelju rezultata notacijske analize, saznali smo da je prosječna prijeđena udaljenost iznosila 113,3±8,6 metara u minuti tijekom jedne utakmice. Prosječna prijeđena udaljenost tijekom utakmice iznosila je 3399±362,3 metra. Najmanja udaljenost (385,8±371,6 m) prijeđena je kategorijom stajanje i hodanje, dok je najveća udaljenost (935,8±165,5) prijeđena kategorijom kaskanje (jogging). Prosječna frekvencija srca iznosila je 183,7±7,3 o/min. Prosječni intenzitet tijekom utakmica bio je 89,6±3,6% od maksimalne frekvencije srca. Rezultati ovog istraživanja pokazuju da je rukomet visokointenzivan diskontinuiran sport. Fiziološki profil igračica tijekom utakmica pokazuje da su igračice provele više od 83% vremena igre u zoni visokog intenziteta (frekvencija srca veća od 85% od maksimalne). Na temelju navedenoga, rukometašicama se preporuča trening usmjeren na anaerobne vježbe koje se provode intervalnom metodom treninga. Anaerobni trening će osigurati kvalitetnu pripremu za uspješnu izvedbu visokointenzivnih aktivnosti tijekom igre, kao i za zadržavanje visoke razine intenziteta igre tijekom cijele utakmice. Zadržavanje visokog intenziteta igre tijekom utakmice najviše ovisi o sposobnosti obnavljanja energetskih izvora tijekom perioda niskointenzivnih aktivnosti. Autori stoga preporučuju rad na unapređenju i anaerobne i aerobne snage tijekom treninga

Dislocations and the critical endpoint of the melting line of vortex line lattices

We develop a theory for dislocation-mediated structural transitions in the vortex lattice which allows for a unified description of phase transitions between the three phases, the elastic vortex glass, the amorphous vortex glass, and the vortex liquid, in terms of a free energy functional for the dislocation density. The origin of a critical endpoint of the melting line at high magnetic fields, which has been recently observed experimentally, is explained.Comment: 4 pages, 1 figur

Practical examination of bystanders performing Basic Life Support in Germany: a prospective manikin study

<p>Abstract</p> <p>Background</p> <p>In an out-of-hospital emergency situation bystander intervention is essential for a sufficient functioning of the chain of rescue. The basic measures of cardiopulmonary resuscitation (Basic Life Support – BLS) by lay people are therefore definitely part of an effective emergency service of a patient needing resuscitation. Relevant knowledge is provided to the public by various course conceptions. The learning success concerning a one day first aid course ("LSM" course in Germany) has not been much investigated in the past. We investigated to what extent lay people could perform BLS correctly in a standardised manikin scenario. An aim of this study was to show how course repetitions affected success in performing BLS.</p> <p>Methods</p> <p>The "LSM course" was carried out in a standardised manner. We tested prospectively 100 participants in two groups (<b>Group 1: </b>Participants with previous attendance of a BLS course; <b>Group 2: </b>Participants with no previous attendance of a BLS course) in their practical abilities in BLS after the course. Success parameter was the correct performance of BLS in accordance with the current ERC guidelines.</p> <p>Results</p> <p>Twenty-two (22%) of the 100 investigated participants obtained satisfactory results in the practical performance of BLS. Participants with repeated participation in BLS obtained significantly better results (<b>Group 1: </b>32.7% vs. <b>Group 2: </b>10.4%; p < 0.01) than course participants with no relevant previous knowledge.</p> <p>Conclusion</p> <p>Only 22% of the investigated participants at the end of a "LSM course" were able to perform BLS satisfactorily according to the ERC guidelines. Participants who had previously attended comparable courses obtained significantly better results in the practical test. Through regular repetitions it seems to be possible to achieve, at least on the manikin, an improvement of the results in bystander resuscitation and, consequently, a better patient outcome. To validate this hypothesis further investigations are recommended by specialised societies.</p

A New Method for the Characterization of Strain-Specific Conformational Stability of Protease-Sensitive and Protease-Resistant PrPSc

Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrPSc, a disease-associated isoform of the host-encoded cellular protein (PrPC). Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrPSc. However, PrPSc is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrPSc aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrPC and PrPSc by means of differential centrifugation. The conformational solubility and stability assay (CSSA) was then developed by measuring PrPSc solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl]1/2 values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl]1/2 values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M), followed by sheep scrapie (2.2 M) and by MM2 sCJD (1.6 M). In order to test the ability of CSSA to characterise protease-sensitive PrPSc, we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrPSc aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrPSc conformational stabilities of protease-resistant and protease-sensitive PrPSc and that it is a valuable tool for strain typing in natural hosts, such as humans and sheep

Molecular Interactions between Prions as Seeds and Recombinant Prion Proteins as Substrates Resemble the Biological Interspecies Barrier In Vitro

Prion diseases like Creutzfeldt-Jakob disease in humans, Scrapie in sheep or bovine spongiform encephalopathy are fatal neurodegenerative diseases, which can be of sporadic, genetic, or infectious origin. Prion diseases are transmissible between different species, however, with a variable species barrier. The key event of prion amplification is the conversion of the cellular isoform of the prion protein (PrPC) into the pathogenic isoform (PrPSc). We developed a sodiumdodecylsulfate-based PrP conversion system that induces amyloid fibril formation from soluble α-helical structured recombinant PrP (recPrP). This approach was extended applying pre-purified PrPSc as seeds which accelerate fibrillization of recPrP. In the present study we investigated the interspecies coherence of prion disease. Therefore we used PrPSc from different species like Syrian hamster, cattle, mouse and sheep and seeded fibrillization of recPrP from the same or other species to mimic in vitro the natural species barrier. We could show that the in vitro system of seeded fibrillization is in accordance with what is known from the naturally occurring species barriers

Detection of Prion Protein Particles in Blood Plasma of Scrapie Infected Sheep

Prion diseases are transmissible neurodegenerative diseases affecting humans and animals. The agent of the disease is the prion consisting mainly, if not solely, of a misfolded and aggregated isoform of the host-encoded prion protein (PrP). Transmission of prions can occur naturally but also accidentally, e.g. by blood transfusion, which has raised serious concerns about blood product safety and emphasized the need for a reliable diagnostic test. In this report we present a method based on surface-FIDA (fluorescence intensity distribution analysis), that exploits the high state of molecular aggregation of PrP as an unequivocal diagnostic marker of the disease, and show that it can detect infection in blood. To prepare PrP aggregates from blood plasma we introduced a detergent and lipase treatment to separate PrP from blood lipophilic components. Prion protein aggregates were subsequently precipitated by phosphotungstic acid, immobilized on a glass surface by covalently bound capture antibodies, and finally labeled with fluorescent antibody probes. Individual PrP aggregates were visualized by laser scanning microscopy where signal intensity was proportional to aggregate size. After signal processing to remove the background from low fluorescence particles, fluorescence intensities of all remaining PrP particles were summed. We detected PrP aggregates in plasma samples from six out of ten scrapie-positive sheep with no false positives from uninfected sheep. Applying simultaneous intensity and size discrimination, ten out of ten samples from scrapie sheep could be differentiated from uninfected sheep. The implications for ante mortem diagnosis of prion diseases are discussed

Impaired Vascular Contractility and Aortic Wall Degeneration in Fibulin-4 Deficient Mice: Effect of Angiotensin II Type 1 (AT1) Receptor Blockade

Medial degeneration is a key feature of aneurysm disease and aortic dissection. In a murine aneurysm model we investigated the structural and functional characteristics of aortic wall degeneration in adult fibulin-4 deficient mice and the potential therapeutic role of the angiotensin (Ang) II type 1 (AT1) receptor antagonist losartan in preventing aortic media degeneration. Adult mice with 2-fold (heterozygous Fibulin-4+/R) and 4-fold (homozygous Fibulin-4R/R) reduced expression of fibulin-4 displayed the histological features of cystic media degeneration as found in patients with aneurysm or dissection, including elastin fiber fragmentation, loss of smooth muscle cells, and deposition of ground substance in the extracellular matrix of the aortic media. The aortic contractile capacity, determined by isometric force measurements, was diminished, and was associated with dysregulation of contractile genes as shown by aortic transcriptome analysis. These structural and functional alterations were accompanied by upregulation of TGF-β signaling in aortas from fibulin-4 deficient mice, as identified by genome-scaled network analysis as well as by immunohistochemical staining for phosphorylated Smad2, an intracellular mediator of TGF-β. Tissue levels of Ang II, a regulator of TGF-β signaling, were increased. Prenatal treatment with the AT1 receptor antagonist losartan, which blunts TGF-β signaling, prevented elastic fiber fragmentation in the aortic media of newborn Fibulin-4R/R mice. Postnatal losartan treatment reduced haemodynamic stress and improved lifespan of homozygous knockdown fibulin-4 animals, but did not affect aortic vessel wall structure. In conclusion, the AT1 receptor blocker losartan can prevent aortic media degeneration in a non-Marfan syndrome aneurysm mouse model. In established aortic aneurysms, losartan does not affect aortic architecture, but does improve survival. These findings may extend the potential therapeutic application of inhibitors of the renin-angiotensin system to the preventive treatment of aneurysm disease

Protease-Resistant Prions Selectively Decrease Shadoo Protein

The central event in prion diseases is the conformational conversion of the cellular prion protein (PrPC) into PrPSc, a partially protease-resistant and infectious conformer. However, the mechanism by which PrPSc causes neuronal dysfunction remains poorly understood. Levels of Shadoo (Sho), a protein that resembles the flexibly disordered N-terminal domain of PrPC, were found to be reduced in the brains of mice infected with the RML strain of prions [1], implying that Sho levels may reflect the presence of PrPSc in the brain. To test this hypothesis, we examined levels of Sho during prion infection using a variety of experimental systems. Sho protein levels were decreased in the brains of mice, hamsters, voles, and sheep infected with different natural and experimental prion strains. Furthermore, Sho levels were decreased in the brains of prion-infected, transgenic mice overexpressing Sho and in infected neuroblastoma cells. Time-course experiments revealed that Sho levels were inversely proportional to levels of protease-resistant PrPSc. Membrane anchoring and the N-terminal domain of PrP both influenced the inverse relationship between Sho and PrPSc. Although increased Sho levels had no discernible effect on prion replication in mice, we conclude that Sho is the first non-PrP marker specific for prion disease. Additional studies using this paradigm may provide insight into the cellular pathways and systems subverted by PrPSc during prion disease