Wrinkling criteria in sheet metal forming for single sided contact situation and its application

The general wrinkling theory based on the rate formulation of the principle of virtual work has been applied in a number of studies on wrinkling during sheet metal forming. No contact with the die was allowed. In this study it is shown that with the right choice of wrinkling modes, the theory can also be used for contact situations. Furthermore, loads normal to the sheet can be taken into account. Therefore, the wrinkling theory has a larger area of application then it was previously considere

On the incidence rate of first overtone Blazhko stars in the Large Magellanic Cloud

By using the full span of multicolor data on a representative sample of first overtone RR Lyrae stars in the Large Magellanic Cloud (LMC) we revisit the problem of the incidence rate of the amplitude/phase-modulated (Blazhko) stars. Multicolor data, obtained by the MAssive Compact Halo Objects (MACHO) project, are utilized through a periodogram averaging method. This enables us to increase the number of detected multiperiodic variables by 18% relative to the number obtained by the analysis of the best single color data. We also test the maximum modulation period detectable in the present dataset. We find that variables showing amplitude/phase modulations with periods close to the total time span can still be clearly separated from the class of stars showing period changes. This larger limit on the modulation period, the more efficient data analysis and the longer time span lead to a substantial increase in the incidence rate of the Blazhko stars in comparison with earlier results. We find altogether 99 first overtone Blazhko stars in the full sample of 1332 stars, implying an incidence rate of 7.5%. Although this rate is nearly twice of the one derived earlier, it is still significantly lower than that of the fundamental mode stars in the LMC. The by-products of the analysis (e.g., star-by-star comments, distribution functions of various quantities) are also presented.Comment: 12 pages, 10 figures, 9 tables, to appear in Astronomy and Astrophysic

Relative Intranuclear Magnesium and Phosphorus Contents in Normal and Tumor Cells of the Human Thyroid Gland as Revealed by Energy-Dispersive X-Ray Microanalysis

Energy dispersive X-ray microanalysis was performed on altogether 42 surgically removed tissue specimens of 32 patients, which were taken either from intact thyroid parts or various histopathologically verified tumors of the thyroid gland. The tissue specimens were processed with the freeze-fracture-freeze-drying technique and then analyzed in the so-called bulk specimen form. The studies were carried out during the years 1980-81, when intranuclear monovalent ionic composition was studied in detail. From the retained total elemental peak list, it was possible to calculate retrospectively the relative intranuclear Mg and P contents. The data processed by nested (hierarchical) analysis of variance show that the intranuclear Mg content of the 5 diagnostic groups (normal thyroid tissue, thyroiditis, benign adenomas, differentiated carcinomas and undifferentiated thyroid tumors) increases significantly, in parallel with the increasing malignancy, but the P content remains unchanged. One can conclude that the elevated intranuclear Mg content in the tumors of high malignancy may be of diagnostic importance, and a warning signal for the therapeutic approaches based on Mg-supplementations

Altered Potassium Ion Homeostasis in Hearing Loss

Connexins, Kv-type ion channels, and pannexins have a dominant role in maintaining the potassium ion homeostasis in the cochlea. The cellular background currents are sustained by Kir2.1 ion channels; however, their involvement in the hearing system is less clear. In this study, the mutations of gap junction proteins beta 2 (GJB2), beta 3 (GJB3) and beta 6 (GJB6) were screened in the white Caucasian population in Hungary using gene mapping and immunofluorescence methods from translated proteins of these genes—connexins on blood cells. Expression of connexins and Kir2.1 ion channels was investigated in the blood cells of deaf patients prior to cochlear implantation, and the results show significantly decreased amounts of connexin26 and connexin43. In addition, the coexpression of Kir2.1 ion channels with synapse-associated 97 proteins was partially impaired. Our investigation revealed a reduced level of Kir2.1 channels in deaf patients indicating a crucial role for the functional Shaker superfamily of K+ channels in the non-diseased hearing system

A versatile transposon-based technology to generate loss- and gain-of-function phenotypes in the mouse liver

Background Understanding the contribution of gene function in distinct organ systems to the pathogenesis of human diseases in biomedical research requires modifying gene expression through the generation of gain- and loss-of-function phenotypes in model organisms, for instance, the mouse. However, methods to modify both germline and somatic genomes have important limitations that prevent easy, strong, and stable expression of transgenes. For instance, while the liver is remarkably easy to target, nucleic acids introduced to modify the genome of hepatocytes are rapidly lost, or the transgene expression they mediate becomes inhibited due to the action of effector pathways for the elimination of exogenous DNA. Novel methods are required to overcome these challenges, and here we develop a somatic gene delivery technology enabling long-lasting high-level transgene expression in the entire hepatocyte population of mice. Results We exploit the fumarylacetoacetate hydrolase (Fah) gene correction-induced regeneration in Fah-deficient livers, to demonstrate that such approach stabilizes luciferase expression more than 5000-fold above the level detected in WT animals, following plasmid DNA introduction complemented by transposon-mediated chromosomal gene transfer. Building on this advancement, we created a versatile technology platform for performing gene function analysis in vivo in the mouse liver. Our technology allows the tag-free expression of proteins of interest and silencing of any arbitrary gene in the mouse genome. This was achieved by applying the HADHA/B endogenous bidirectional promoter capable of driving well-balanced bidirectional expression and by optimizing in vivo intronic artificial microRNA-based gene silencing. We demonstrated the particular usefulness of the technology in cancer research by creating a p53-silenced and hRas G12V-overexpressing tumor model. Conclusions We developed a versatile technology platform for in vivo somatic genome editing in the mouse liver, which meets multiple requirements for long-lasting high-level transgene expression. We believe that this technology will contribute to the development of a more accurate new generation of tools for gene function analysis in mice.Peer reviewe

Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian (Hungarian) sample

BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1alpha) is a transcription factor that plays an important role in neo-vascularisation, embryonic pancreas beta-cell mass development, and beta cell protection. Recently a non synonymous single nucleotide polymorphism (g.C45035T SNP, rs11549465) of HIF-1alpha gene, resulting in the p.P582S amino acid change has been shown to be associated with type 2 diabetes (T2DM) in a Japanese population. Our aim was to replicate these findings on a Caucasian (Hungarian) population, as well as to study whether this genetic effect is restricted to T2DM or can be expanded to diabetes in general. METHODS: A large Caucasian sample (N = 890) was recruited including 370 T2DM, 166 T1DM and 354 healthy subjects. Genotyping was validated by two independent methods: a restriction fragment analysis (RFLP) and a real time PCR using TaqMan probes. An overestimation of heterozygotes by RFLP was observed as a consequence of a nearby SNP (rs34005929). Therefore genotyping results of the justified TaqMan system were accepted. The measured genotype distribution corresponded to Hardy-Weinberg equilibrium (P = 0.740) RESULTS: As the TT genotype was extremely rare in the population (0.6% in clinical sample and 2.5% in controls), the genotypes were grouped as T absent (CC) and T present (CT and TT). Genotype-wise analysis showed a significant increase of T present group in controls (24.0%) as compared to patients (16.8%, P = 0.008). This genetic effect was demonstrated in the separated samples of type 1 (15.1%, P = 0.020), and also in type 2 (17.6%, P = 0.032) diabetes. Allele-wise analysis gave identical results showing a higher frequency of the T allele in the control sample (13.3%) than in the clinical sample (8.7%, P = 0.002) with similar results in type 1 (7.8%, P = 0.010) and type 2 (9.1%, P = 0.011) diabetes. The odds ratio for diabetes (either type 1 or 2) was 1.56 in the presence of the C allele. CONCLUSION: We confirmed the protective effect of a rare genetic variant of HIF-1alpha gene against type 2 diabetes in a Caucasian sample. Moreover we demonstrated a genetic contribution of the same polymorphism in type 1 diabetes as well, supporting a possible overlap in pathomechanism for T2DM and a T1DM

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

POTENTIAL FOR HUNGARIAN GRASSLANDS IN INTEGRATED RURAL DEVELOPMENT

Sustainability and multifunctionality, two key principles, which will determine future development in any activities. On the bases of these principles, society as a whole has already outlined future expectations towards rural areas. Rural functions (economic, ecological and socio-cultural ones) have been declared in European Charter for Rural Areas. To what extend can different rural development initiatives meet these functions? The question may be answered by using the method of multifunctional rural resource analysis (NAGY, 2007). The paper is investigating the potential for Hungarian grasslands by using this methodology. It is concluded that our grasslands, as land use systems in their present conditions can participate in integrated rural development in the most balanced way compared to other land use systems in the county. Economically their potential is good. Ecologically their potential is outstanding. The socio-cultural potential of grassland use in Hungary is also outstanding due to the historical roots. As a future prediction the relative importance of the three grassland functions has been outlined in integrated agriculture and rural development

POTENTIAL FOR HUNGARIAN GRASSLANDS IN INTEGRATED RURAL DEVELOPMENT

Sustainability and multifunctionality, two key principles, which will determine future development in any activities. On the bases of these principles, society as a whole has already outlined future expectations towards rural areas. Rural functions (economic, ecological and socio-cultural ones) have been declared in European Charter for Rural Areas. To what extend can different rural development initiatives meet these functions? The question may be answered by using the method of multifunctional rural resource analysis (NAGY, 2007). The paper is investigating the potential for Hungarian grasslands by using this methodology. It is concluded that our grasslands, as land use systems in their present conditions can participate in integrated rural development in the most balanced way compared to other land use systems in the county. Economically their potential is good. Ecologically their potential is outstanding. The socio-cultural potential of grassland use in Hungary is also outstanding due to the historical roots. As a future prediction the relative importance of the three grassland functions has been outlined in integrated agriculture and rural development.sustainability, multifunctionality, grasslands, future potential, Agricultural and Food Policy, Community/Rural/Urban Development, Land Economics/Use,