History-dependent domain and skyrmion formation in 2D van der Waals magnet Fe3GeTe2.

The discovery of two-dimensional magnets has initiated a new field of research, exploring both fundamental low-dimensional magnetism, and prospective spintronic applications. Recently, observations of magnetic skyrmions in the 2D ferromagnet Fe3GeTe2 (FGT) have been reported, introducing further application possibilities. However, controlling the exhibited magnetic state requires systematic knowledge of the history-dependence of the spin textures, which remains largely unexplored in 2D magnets. In this work, we utilise real-space imaging, and complementary simulations, to determine and explain the thickness-dependent magnetic phase diagrams of an exfoliated FGT flake, revealing a complex, history-dependent emergence of the uniformly magnetised, stripe domain and skyrmion states. The results show that the interplay of the dominant dipolar interaction and strongly temperature dependent out-of-plane anisotropy energy terms enables the selective stabilisation of all three states at zero field, and at a single temperature, while the Dzyaloshinksii-Moriya interaction must be present to realise the observed Néel-type domain walls. The findings open perspectives for 2D devices incorporating topological spin textures.

Metal abundances in hot white dwarfs with signatures of a superionized wind.

About a dozen hot white dwarfs with effective temperatures T eff = 65 000 K - 120 000 K exhibit unusual absorption features in their optical spectra. These objects were tentatively identified as Rydberg lines of ultra-high excited metals in ionization stages v-x, indicating line formation in a dense environment with temperatures near 106 K. Since some features show blueward extensions, it was argued that they stem from a superionized wind. A unique assignment of the lines to particular elements is not possible, although they probably stem from C, N, O, and Ne. To further investigate this phenomenon, we analyzed the ultraviolet spectra available from only three stars of this group; that is, two helium-rich white dwarfs, HE 0504-2408 and HS 0713+3958 with spectral type DO, and a hydrogen-rich white dwarf, HS 2115+1148 with spectral type DAO. We identified light metals (C, N, O, Si, P, and S) with generally subsolar abundances and heavy elements from the iron group (Cr, Mn, Fe, Co, Ni) with solar or oversolar abundance. The abundance patterns are not unusual for hot WDs and can be interpreted as the result of gravitational settling and radiative levitation of elements. As to the origin of the ultra-high ionized metals lines, we discuss the possible presence of a multicomponent radiatively driven wind that is frictionally heated.

Topological Crystalline Insulator in a New Bi Semiconducting Phase.

Topological crystalline insulators are a type of topological insulators whose topological surface states are protected by a crystal symmetry, thus the surface gap can be tuned by applying strain or an electric field. In this paper we predict by means of ab initio calculations a new phase of Bi which is a topological crystalline insulator characterized by a mirror Chern number nM = -2, but not a strong topological insulator. This system presents an exceptional property: at the (001) surface its Dirac cones are pinned at the surface high-symmetry points. As a consequence they are also protected by time-reversal symmetry and can survive against weak disorder even if in-plane mirror symmetry is broken at the surface. Taking advantage of this dual protection, we present a strategy to tune the band-gap based on a topological phase transition unique to this system. Since the spin-texture of these topological surface states reduces the back-scattering in carrier transport, this effective band-engineering is expected to be suitable for electronic and optoelectronic devices with reduced dissipation.

Safety, pharmacokinetics and pharmacodynamics of BI 135585, a selective 11ß-hydroxysteroid dehydrogenase-1 (HSD1) inhibitor in humans: liver and adipose tissue 11ß-HSD1 inhibition after acute and multiple administrations over 2 weeks.

AIMS: To assess the safety and pharmacokinetic and pharmacodynamic characteristics of BI 135585, a selective 11ß-hydroxysteroid dehydrogenase-1 (11ß-HSD1) inhibitor, after single- and repeated-dose administration. METHODS: The single-dose study included open-label administration of 200 mg BI 135585 in healthy volunteers, while in the multiple-dose study, we carried out randomized, double-blind administration of 5-200 mg BI 135585 or placebo once daily over 14 days in patients with type 2 diabetes (T2DM). Assessments included 11ß-HSD1 inhibition in the liver (urinary tetrahydrocortisol (THF)/tetrahydrocotisone (THE) ratio) and in subcutaneous adipose tissue (AT) ex vivo and determination of hypothalamus-pituitary-adrenal (HPA) axis hormone levels. RESULTS: No major safety issues occurred with BI 135585 administration. The HPA axis was mildly activated with slightly increased, but still normal adrenocorticotropic hormone levels, increased total urinary corticoid excretion but unchanged plasma cortisol levels. After multiple doses of 5-200 mg BI 135585, exposure (area under the curve) increased dose-proportionally and half-life was 55-65 h. The urinary THF/THE ratio decreased, indicating liver 11ß-HSD1 inhibition. Median 11ß-HSD1 enzyme inhibition in the AT reached 90% after a single dose of BI 135585, but was low (31% or lower) after 14 days of continuous treatment. CONCLUSIONS: BI 135585 was safe and well tolerated over 14 days and can be dosed once daily. Future studies are required to clarify the therapeutic potential of BI 135585 in view of its effects on 11ß-HSD1 inhibition in AT after single and multiple doses. Enzyme inhibition in the AT was not adequately predicted by the urinary THF/THE ratio.

Disease-promoting and -protective genomic loci on mouse chromosomes 3 and 19 control the incidence and severity of autoimmune arthritis.

Proteoglycan (PG)-induced arthritis (PGIA) is a murine model of rheumatoid arthritis. Arthritis-prone BALB/c mice are 100% susceptible, whereas the major histocompatibility complex-matched DBA/2 strain is completely resistant to PGIA. To reduce the size of the disease-suppressive loci for sequencing and to find causative genes of arthritis, we created a set of BALB/c.DBA/2-congenic/subcongenic strains carrying DBA/2 genomic intervals overlapping the entire Pgia26 locus on chromosome 3 (chr3) and Pgia23/Pgia12 loci on chr19 in the arthritis-susceptible BALB/c background. Upon immunization of these subcongenic strains and their wild-type (BALB/c) littermates, we identified a major Pgia26a sublocus on chr3 that suppressed disease onset, incidence and severity via controlling the complex trait of T-cell responses. The region was reduced to 3 Mbp (11.8 Mbp with flanking regions) in size and contained gene(s) influencing the production of a number of proinflammatory cytokines. Additionally, two independent loci (Pgia26b and Pgia26c) suppressed the clinical scores of arthritis. The Pgia23 locus (∼3 Mbp in size) on chr19 reduced arthritis susceptibility and onset, and the Pgia12 locus (6 Mbp) associated with low arthritis severity. Thus, we have reached the critical sizes of arthritis-associated genomic loci on mouse chr3 and chr19, which are ready for high-throughput sequencing of genomic DNA.

T cell receptor (TCR) signal strength controls arthritis severity in proteoglycan-specific TCR transgenic mice.

T cell receptor transgenic (TCR-Tg) mice specific for the arthritogenic 5/4E8 epitope in the G1 domain of cartilage proteoglycan were generated and back-crossed into arthritis-prone BALB/c background. Although more than 90% of CD4(+) T cells of all TCR-Tg lines were 5/4E8-specific, one (TCR-TgA) was highly sensitive to G1-induced or spontaneous arthritis, while another (TCR-TgB) was less susceptible. Here we studied whether fine differences in TCR signalling controlled the onset and severity of arthritis. Mice from the two TCR-Tg lines were immunized side by side with purified recombinant human G1 (rhG1) domain for G1 domain of cartilage proteoglycan (PG)-induced arthritis (GIA). TCR-TgA mice developed severe and early-onset arthritis, whereas TCR-TgB mice developed weaker arthritis with delayed onset, although TCR-TgB CD4(+) T cells expressed approximately twice more TCR-Vß4 chain protein. The more severe arthritis in TCR-TgA mice was associated with higher amounts of anti-G1 domain-specific antibodies, larger numbers of B cells and activated T helper cells. Importantly, TCR-TgB CD4(+) T cells were more sensitive to in vitro activation-induced apoptosis, correlating with their higher TCR and CD3 expression and with the increased TCR signal strength. These findings indicate that TCR signal strength determines the clinical outcome of arthritis induction: 'optimal' TCR signal strength leads to strong T cell activation and severe arthritis in TCR-TgA mice, whereas 'supra-optimal' TCR signal leads to enhanced elimination of self-reactive T cells, resulting in attenuated disease.

Osteoarthritis-like damage of cartilage in the temporomandibular joints in mice with autoimmune inflammatory arthritis.

OBJECTIVE: To study temporomandibular joint (TMJ) involvement in an autoimmune murine model of rheumatoid arthritis (RA), a disease characterized by inflammatory destruction of the synovial joints. Although TMJ dysfunction is frequently found in RA, TMJ involvement in RA remains unclear, and TMJ pathology has not been studied in systemic autoimmune animal models of RA. METHODS: Proteoglycan (PG) aggrecan-induced arthritis (PGIA) was generated in genetically susceptible BALB/c mice. TMJs and joint tissues/cartilage were harvested for histological and immunohistochemical analyses and RNA isolation for quantitative polymerase chain-reaction. Serum cytokine levels were measured in mice with acute or chronic arthritis, and in non-arthritic control animals. RESULTS: Despite the development of destructive synovitis in the limbs, little or no synovial inflammation was found in the TMJs of mice with PGIA. However, the TMJs of arthritic mice showed evidence of aggrecanase- and matrix metalloproteinase-mediated loss of glycosaminoglycan-containing aggrecan, and in the most severe cases, structural damage of cartilage. Serum levels of pro-inflammatory cytokines, including interleukin (IL)-1ß, were elevated in arthritic animals. Expression of the IL-1ß gene was also high in the inflamed limbs, but essentially normal in the TMJs. Local expression of genes encoding matrix-degrading enzymes (aggrecanases and stromelysin) was upregulated to a similar degree in both the limbs and the TMJs. CONCLUSION: We propose that constantly elevated levels of catabolic cytokines, such as IL-1ß, in the circulation (released from inflamed joints) create a pro-inflammatory milieu within the TMJ, causing local upregulation of proteolytic enzymes and subsequent loss of aggrecan from cartilage.

Low temperature of GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor DnaK.

Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly synthesized proteins. The combined deletion of the TF-encoding tig gene and the dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C. Here we show that the synthetic lethality of deltatigdeltadnaK52 cells is abrogated either by growth below 30 degrees C or by overproduction of GroEL/GroES. At 23 degrees C deltatigdeltadnaK52 cells were viable and showed only minor protein aggregation. Overproduction of GroEL/GroES, but not of other chaperones, restored growth of deltatigdeltadnaK52 cells at 30 degrees C and suppressed protein aggregation including proteins >/= 60 kDa, which normally require TF and DnaK for folding. GroEL/GroES thus influences the folding of proteins previously identified as DnaK/TF substrates.

Removal mechanisms of endocrine disrupting compounds (steroids) during soil aquifer treatment.

The objective of this study was to determine the primary removal mechanisms of endocrine disruptors such as steroidal hormones present in reclaimed water, specifically 17beta-estradiol, estriol, and testosterone, during groundwater recharge via soil aquifer treatment (SAT). Steroidal hormones were quantified using enzyme-linked immunosorbent assays. Bench-scale studies and laboratory-scale soil column experiments were employed to determine what mechanisms (i.e., adsorption, biodegradation, photolytic degradation) dominate the removal of the three compounds of interest during SAT. Findings of these studies revealed that the dominating removal mechanism for the compounds of interest during SAT is adsorption to the porous media matrix and additional attenuation to below the detection limit occurred in the presence of bioactivity. This additional removal occurred regardless of dominating redox conditions (aerobic vs. anoxic) or the type of organic carbon matrix present (hydrophobic acids, hydrophilic carbon vs. colloidal carbon).

Assessing the removal potential of soil-aquifer treatment systems for bulk organic matter.

The fate of effluent organic matter (EfOM) during groundwater recharge was investigated by studying the removal behavior of four bulk organic carbon fractions isolated from a secondary effluent: Hydrophilic organic matter (HPI), hydrophobic acids (HPO-A), colloidal organic matter (OM), and soluble microbial products (SMPs). Short-term removal of the bulk organic fractions during soil infiltration was simulated in biologically active soil columns. Results revealed that the four organic fractions showed a significantly different behavior with respect to biological removal. HPI and colloidal OM were prone to biological removal during initial soil infiltration (0-30 cm) and supported soil microbial biomass growth in the infiltrative surface. Additionally, colloidal OM was partly removed by physical adsorption or filtration. HPO-A and SMPs reacted recalcitrant towards biological degradation as indicated by low soil biomass activity responses. Adsorbability assessment of the biologically refractory portions of the fractions onto powered activated carbon (PAC) indicated that physical removal is not likely to play a significantly role in further diminishing recalcitrant HPO-A, HPI and SMPs during longer travel times in the subsurface.

Functional dissection of Escherichia coli trigger factor: unraveling the function of individual domains.

In Escherichia coli, the ribosome-associated chaperone Trigger Factor (TF) promotes the folding of newly synthesized cytosolic proteins. TF is composed of three domains: an N-terminal domain (N), which mediates ribosome binding; a central domain (P), which has peptidyl-prolyl cis/trans isomerase activity and is involved in substrate binding in vitro; and a C-terminal domain (C) with unknown function. We investigated the contributions of individual domains (N, P, and C) or domain combinations (NP, PC, and NC) to the chaperone activity of TF in vivo and in vitro. All fragments comprising the N domain (N, NP, NC) complemented the synthetic lethality of Deltatig DeltadnaK in cells lacking TF and DnaK, prevented protein aggregation in these cells, and cross-linked to nascent polypeptides in vitro. However, DeltatigDeltadnaK cells expressing the N domain alone grew more slowly and showed less viability than DeltatigDeltadnaK cells synthesizing either NP, NC, or full-length TF, indicating beneficial contributions of the P and C domains to TF's chaperone activity. In an in vitro system with purified components, none of the TF fragments assisted the refolding of denatured d-glyceraldehyde-3-phosphate dehydrogenase in a manner comparable to that of wild-type TF, suggesting that the observed chaperone activity of TF fragments in vivo is dependent on their localization at the ribosome. These results indicate that the N domain, in addition to its function to promote binding to the ribosome, has a chaperone activity per se and is sufficient to substitute for TF in vivo.

Low temperature or GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor and DnaK.

Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly synthesized proteins. The combined deletion of the TF-encoding tig gene and the dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C. Here we show that the synthetic lethality of DeltatigDeltadnaK52 cells is abrogated either by growth below 30 degrees C or by overproduction of GroEL/GroES. At 23 degrees C DeltatigDeltadnaK52 cells were viable and showed only minor protein aggregation. Overproduction of GroEL/GroES, but not of other chaperones, restored growth of DeltatigDeltadnaK52 cells at 30 degrees C and suppressed protein aggregation including proteins >/=60 kDa, which normally require TF and DnaK for folding. GroEL/GroES thus influences the folding of proteins previously identified as DnaK/TF substrates.

How to find the real one (at the level of pre-mRNA splicing).

The mature mRNA always carries nucleotide sequences that faithfully mirror the protein product according to the niles of the genetic code. However, in the chromosome, the nucleotide sequence that represents a certain protein is interrupted by additional sequences. Therefore, most eukaryotic genes are longer than their final mRNA products. The human genome project revealed that only a tiny portion of sequences serves as protein-coding region and almost one quarter of the genome is occupied by non-coding intervening sequences. The elimination of these non-coding regions from the precursor RNA in a process termed splicing must be extremely precise, because even a single nucleotide mistake may cause a fatal error. At present, two types of intervening sequences have been identified in protein-coding genes. One of them, the U2-dependent or major-class is prevalent and represents 99% of known sequences. The other one, the so-called U12-dependent or minor-class of introns, occurs in much lesser amounts in the genome. The basic problem of nuclear splicing concerns i/ the molecular mechanisms, which ensure that the coding regions are correctly recognized and spliced together: ii/ the principles and mechanisms that guarantee the high fidelity of the splicing system; iii/ the differences in the excision mechanisms of the two classes of introns. We are going to present models explaining how intervening sequences are accurately removed and the coding regions correctly juxtaposed. The two splicing mechanisms will also be compared.

Effectiveness of two radiofrequency ablation systems in atrial tissue.

OBJECTIVE: The efficacy of the left atrial radiofrequency ablation procedure, for the curative treatment of atrial fibrillation, is dependent upon obtaining a confluent transmural line of hyperthermic cellular death. We compare the in vitro effectiveness of obtaining transmural hyperthermic cellular death (>55 degrees C) of both the Osypka single electrode and Boston Scientific Thermaline multi-electrode radiofrequency systems. METHODS: Isolated cadaver porcine hearts were used to measure epicardial temperatures either 'central' or at the 'edge' in relation to an endocardial applied radiofrequency electrode. Reference set point was 70 degrees C, and 4-6-mm thick atrial tissue was used for all applications. 'Edge' temperatures with the Boston Scientific unit were measured whilst activating both adjacent electrodes. RESULTS: Boston Scientific: Probe temperature closely approximated the set point. 'Central' epicardial temperature was lower than probe temperature until after 40 s application (P<0.05), 55 degrees C was reached at 50 s, maximal mean temperature 63.0+/-8.9 degrees C was reached at 100 s. Epicardial 'edge' temperature remained lower than probe temperature for the entire 120 s (P<0.05). Osypka: Probe temperature tended to overshoot the set point. 'Central' epicardial temperature paralleled and occasionally exceeded probe temperature reaching 55 degrees C within 10 s, maximal mean temperature 76.3+/-12.7 degrees C was reached at 10 s and exceeded the set point thereafter. 'Edge' temperature was no different to probe temperature or 'central' epicardial temperature. The mean epicardial temperatures produced with a 65 degrees C set point was no different to that with the 70 degrees C set point, except for a lower final temperature at 60 s. CONCLUSIONS: The Boston Scientific system (70 degrees C set point) requires a minimum in vitro application of 40 s to transmurally increase 4-6 mm atrial tissue temperature above 55 degrees C, and 120-s duration per application would appear to be a reasonable clinical recommendation. The Osypka system transfers thermal energy more effectively, requiring less than 10 s in vitro to achieve a similar transmural temperature, and a 30-s application can be recommended. However, a tendency to overshoot both probe and set point temperature, suggests that a lower set point of 65 degrees C might be safer and as effective.

Extracellular matrix gene expression correlates to left ventricular mass index after surgical induction of left ventricular hypertrophy.

The cardiac extracellular matrix (ECM) is a dynamic entity maintaining the structural and functional properties of the myocardium. Little is known about alterations in ECM regulation during controlled induction of compensated left ventricular hypertrophy (LVH) using experimental aortic stenosis. Fifteen growing sheep received supra-coronary banding at an age of 7 +/- 1 months whereas 10 age-matched sheep served as the control group (C). Explantation of the hearts was performed 8.3 +/- 1 months after banding. Gene sequences for sheep matrix metalloproteinase (MMP)-1,-2,-3,-9 and tissue inhibitors (TIMP)-1,-2,-3 were isolated and cloned. Then mRNA and protein gene expression analyses were performed. Concentric LVH with no evidence of heart failure was diagnosed at explantation. Left ventricular mass index (LVMI) was 150 +/- 33 g/m2 (LVH) versus 88 +/- 23 (C) and 82 +/- 21 (baseline) (p < 0.01 versus LVH). Parallel to LVH there was a significant increase in mRNA and protein expression for MMP-1,-2,-3, -9 and for TIMP-1,-2 whereas there was a significant decrease in TIMP-3 gene expression. A close correlation between changes in LVMI and ECM gene expression was found. Compensated LVH goes along with a significant modification of MMP and TIMP gene expression. Alterations in ECM gene expression may be part of the adaptive process during left ventricular remodeling.

A new intracardiac microaxial pump: first results of a multicenter study.

As coronary artery bypass grafting (CABG) surgery in the beating heart technique is progressing, new devices have been developed to overcome hemodynamic instabilities while tilting the heart for exposure of back wall vessels. A new device for in heart biventricular intracorporeal circulation was applied in 42 patients undergoing CABG surgery (Group 1). The control group consisted of 38 patients operated on using a conventional cardiopulmonary bypass setup (Group 2). The study protocol of the prospective, randomized multicenter study was approved by the local ethics committees. Patients were included following inclusion criteria and patient informed consent. Mean age, procedure time, mean arterial pressure (MAP), and hemolysis by means of plasma free hemoglobin (fHb) were assessed preoperatively, perioperatively, on postoperative Days 1 to 3, at discharge, and at a 3 month follow-up. The mean age was 62.1 (range 59-74) years (Group 1), 62.7 (range 48-72) years (Group 2); procedure time was 112 min +/- 31.9 min (Group 1), 137.4 min +/- 36.2 min (Group 2); and 2.3 +/- 0.6 (Group 1), 2.2 +/- 0.7 (Group 2), vessels were revascularized. The flow on pump was 3.7 (2.5/4.4) L/min (Group 1), 4.9 (3.6/6.2) L/min (Group 2) which resulted in a MAP of 69.8 (4.0/143) mm Hg (Group 1), 58.3 (5.3/94) mm Hg while assessing the vessels of the back wall. Hemolysis defined by fHB was lower than 20 mg/dl at all times pre- and postoperatively. Intraoperative maximum values were up to 100 mg/dl in 4 patients (2 in Group 1 and 2 in Group 2). Body mass index was 26.4 +/- 2.6 (Group 1), 27.9 +/- 3.2. New York Heart Association Class was II to III in both groups. There were no pump related life threatening or severe adverse events. Beating heart procedures with ICC can be reliably and safely achieved. As the device is easy to use, it may deserve a more widespread use in the future.

[Robotic surgery--surgical and anesthesiologic implications]. / Operationsroboter--Chirurgische und anästhesiologische Implikationen.

Because of the restricted freedom of movement inherent in endoscopic standard instruments wholly endoscopic heart surgery has not been possible up to now. The development of such techniques was especially hindered by the rib cage. Now the precision which is imperative for bypass surgery or valve reconstruction is made possible by telemanipulator systems. Preconditions for this method are cardiopulmonary bypass-techniques which allow a cardioplegic cardiac arrest with closed chest and extensive hemodynamic monitoring which enables the anesthesiologist to make exact diagnoses without having a direct view on the heart. After an extensive experimental phase a telemanipulation system is successfully in use since May 1998 in the Cardiac Center in Leipzig.

[Patient-adapted valve selection: biological vs. mechanical heart valve replacement in aortic valve diseases]. / Patientenadaptierte Klappenselektion: biologischer vs. mechanischer Herzklappenersatz bei Aortenklappenvitien.

Since the first aortic valve replacement performed by Harken in 1960, the operation of aortic valve disease by replacing the native valve with a heart valve prosthesis has become one of the most frequently performed procedures in cardiac surgery. For valve replacement there are biological (xenografts and homografts) and mechanical heart valve prostheses available. When choosing the most suitable prosthesis the limited durability of a biological prosthesis and the risks of lifelong anticoagulation for a mechanical prosthesis have to be balanced. In this article the indication for operation of aortic valve stenosis and aortic regurgitation are discussed first. Based on the literature of the last 2 years the advantages and disadvantages of mechanical and biological heart valve prostheses (xenograft, homograft and ROSS procedure) are discussed. In addition rarely used techniques like aortic valve reconstruction are presented. Due to the fact that a biological prosthesis has a durability of 12-15 years and the risk of bleeding complications under anticoagulation grows with increasing age, the choice of a biological prosthesis can be recommended from the age of 65 years. Results of long-term studies at to whether this limit can be diminished by using a stentless biological prosthesis have to be awaited.

[Patient adapted valve selection: biological vs. mechanical heart valve replacement in aortic valve diseases]. / Patientenadaptierte Klappenselektion: biologischer vs. mechanischer Herzklappenersatz bei Aortenklappenvitien.

Since the first aortic valve replacement performed by Harken in 1960, the operation of aortic valve disease by replacing the native valve with a heart valve prosthesis has become one of the most frequently performed procedures in cardiac surgery. For valve replacement there are biological (xenografts and homografts) and mechanical heart valve prostheses available. When choosing the most suitable prosthesis the limited durability of a biological prosthesis and the risks of lifelong anticoagulation for a mechanical prosthesis have to be balanced.In this article the indication for operation of aortic valve stenosis and aortic regurgitation are discussed first. Based on the literature of the last 2 years the advantages and disadvantages of mechanical and biological heart valve prostheses (xenograft, homograft and ROSS procedure) are discussed. In addition rarely used techniques like aortic valve reconstruction are presented.Due to the fact that a biological prosthesis has a durability of 12-15 years and the risk of bleeding complications under anticoagulation grows with increasing age, the choice of a biological prosthesis can be recommended from the age of 65 years. Results of long-term studies at to whether this limit can be diminished by using a stentless biological prosthesis have to be awaited.