О противодействии недружественным слияниям и поглощениям в сельском хозяйстве

Целью данной работы является определение путей повышения эффективности противодействия рейдерству в аграрной сфере Украины

A semantic interoperability approach to support integration of gene expression and clinical data in breast cancer

[Abstract] Introduction. The introduction of omics data and advances in technologies involved in clinical treatment has led to a broad range of approaches to represent clinical information. Within this context, patient stratification across health institutions due to omic profiling presents a complex scenario to carry out multi-center clinical trials. Methods. This paper presents a standards-based approach to ensure semantic integration required to facilitate the analysis of clinico-genomic clinical trials. To ensure interoperability across different institutions, we have developed a Semantic Interoperability Layer (SIL) to facilitate homogeneous access to clinical and genetic information, based on different well-established biomedical standards and following International Health (IHE) recommendations. Results. The SIL has shown suitability for integrating biomedical knowledge and technologies to match the latest clinical advances in healthcare and the use of genomic information. This genomic data integration in the SIL has been tested with a diagnostic classifier tool that takes advantage of harmonized multi-center clinico-genomic data for training statistical predictive models. Conclusions. The SIL has been adopted in national and international research initiatives, such as the EURECA-EU research project and the CIMED collaborative Spanish project, where the proposed solution has been applied and evaluated by clinical experts focused on clinico-genomic studies.Instituto de Salud Carlos III, PI13/02020Instituto de Salud Carlos III, PI13/0028

A Polymorphism Affecting MYB Binding within the Promoter of the PDCD4 Gene is Associated with Severe Asthma in Children

A previous genome-wide association study in asthma revealed putative associations that merit further investigation. In this study, the genome-wide significant associations of SNPs at the 5% false discovery rate were examined in independent groups of severe asthmatics. The panel consisted of 397 severe asthmatic adults, 116 severe asthmatic children, and a collection of 207 family-trios with an asthmatic proband. Three SNPs in the PDCD4 gene (rs6585018:G>A, rs1322997:C>A, and rs34104444:G>A) were significantly associated with severe childhood asthma (P values: 0.003, 0.002, 0.004) and total immunoglobulin E (IgE) levels (P values: 0.034, 0.041, 0.052). In an independent group of 234 asthmatic children and 652 controls, PDCD4 SNPs rs1407696:T>G and rs11195360:T>C were associated with total IgE levels (P values: 0.006, 0.014). In silico analysis of PDCD4 locus showed that rs6585018:G>A had the potential to affect MYB transcription factor binding, shown to act as a PDCD4-transcription inducer. Electromobility shift assays and reporter assays revealed that rs6585018:G>A alters MYB binding thereby influencing the expression of PDCD4. SNPs within MYB itself confer susceptibility to eosinophilia and asthma. Our association between a variant MYB binding site in PDCD4 and the severest form of childhood asthma therefore suggests that PDCD4 is a novel molecule of importance to asthmatic inflammatory responses

Multi-frequency VEMPs improve detection of present otolith responses in bilateral vestibulopathy

ObjectiveTo investigate whether multi-frequency Vestibular Evoked Myogenic Potential (VEMP) testing at 500, 750, 1,000, and 2,000 Hz, would improve the detection of present dynamic otolith responses in patients with bilateral vestibulopathy (BV).MethodsProspective study in a tertiary referral center. BV patients underwent multi-frequency VEMP testing. Cervical VEMPs and ocular VEMPs were recorded with the Neuro-Audio system (v2010, Neurosoft, Ivanovo, Russia). The stimuli included air-conducted tone bursts of 500, 750, 1,000, and 2,000 Hz, at a stimulation rate of 13 Hz. Outcome measures included the percentage of present and absent VEMP responses, and VEMP thresholds. Outcomes were compared between frequencies and type of VEMPs (cVEMPs, oVEMPs). VEMP outcomes obtained with the 500 Hz stimulus, were also compared to normative values obtained in healthy subjects.ResultsForty-nine BV patients completed VEMP testing: 47 patients completed cVEMP testing and 48 patients completed oVEMP testing. Six to 15 % more present VEMP responses were obtained with multifrequency testing, compared to only testing at 500 Hz. The 2,000 Hz stimulus elicited significantly fewer present cVEMP responses (right and left ears) and oVEMP responses (right ears) compared to the other frequencies (p ≤ 0.044). Using multi-frequency testing, 78% of BV patients demonstrated at least one present VEMP response in at least one ear. In 46% a present VEMP response was found bilaterally. BV patients demonstrated a significantly higher percentage of absent VEMP responses and significantly higher VEMP thresholds than healthy subjects, when corrected for age (p ≤ 0.002). Based on these results, a pragmatic VEMP testing paradigm is proposed, taking into account multi-frequency VEMP testing.ConclusionMulti-frequency VEMP testing improves the detection rate of present otolith responses in BV patients. Therefore, multi-frequency VEMPs should be considered when evaluation of (residual) otolith function is indicated

The evolutionary state of Miras with changing pulsation periods

Context: Miras are long-period variables thought to be in the asymptotic giant branch (AGB) phase of evolution. In about one percent of known Miras, the pulsation period is changing. It has been speculated that this changing period is the consequence of a recent thermal pulse in these stars. Aims: We aim to clarify the evolutionary state of these stars, and to determine in particular whether or not they are in the thermally-pulsing (TP-)AGB phase. Methods: One important piece of information that has been neglected so far when determining the evolutionary state is the presence of the radio-active s-process element technetium (Tc). We obtained high-resolution, high signal-to-noise-ratio optical spectra of a dozen prominent Mira variables with changing pulsation period to search for this indicator of TPs and dredge-up. We also use the spectra to measure lithium (Li) abundances. Furthermore, we establish the evolutionary states of our sample stars by means of their present-day periods and luminosities. Results: Among the twelve sample stars observed in this programme, five were found to show absorption lines of Tc. BH Cru is found to be a carbon-star, its period increase in the past decades possibly having stopped by now. We report a possible switch in the pulsation mode of T UMi from Mira-like to semi-regular variability in the past two years. R Nor, on the other hand, is probably a fairly massive AGB star, which could be true for all meandering Miras. Finally, we assign RU Vul to the metal-poor thick disk with properties very similar to the short-period, metal-poor Miras. Conclusions: We conclude that there is no clear correlation between period change class and Tc presence. The stars that are most likely to have experienced a recent TP are BH Cru and R Hya, although their rates of period change are quite different.Comment: 11 pages, 7 figures, 2 tables; accepted for publication in A&

Effect of Cu and Sn promotion on the catalytic deoxygenation of model and algal lipids to fuel-like hydrocarbons over supported Ni catalysts

The ability of Cu and Sn to promote the performance of a 20% Ni/Al2O3 catalyst in the deoxygenation of lipids to fuel-like hydrocarbons was investigated using model triglyceride and fatty acid feeds, as well as algal lipids. In the semi-batch deoxygenation of tristearin at 260 °C a pronounced promotional effect was observed, a 20% Ni-5% Cu/Al2O3 catalyst affording both higher conversion (97%) and selectivity to C10-C17 alkanes (99%) in comparison with unpromoted 20% Ni/Al2O3 (27% conversion and 87% selectivity to C10-C17). In the same reaction at 350 °C, a 20% Ni-1% Sn/Al2O3 catalyst afforded the best results, giving yields of C10-C17 and C17 of 97% and 55%, respectively, which contrasts with the corresponding values of 87 and 21% obtained over 20% Ni/Al2O3. Equally encouraging results were obtained in the semi-batch deoxygenation of stearic acid at 300 °C, in which the 20% Ni-5% Cu/Al2O3 catalyst afforded the highest yields of C10-C17 and C17. Experiments were also conducted at 260 °C in a fixed bed reactor using triolein − a model unsaturated triglyceride − as the feed. While both 20% Ni/Al2O3 and 20% Ni-5% Cu/Al2O3 achieved quantitative yields of diesel-like hydrocarbons at all reaction times sampled, the Cu-promoted catalyst exhibited higher selectivity to longer chain hydrocarbons, a phenomenon which was also observed in experiments involving algal lipids as the feed. Characterization of fresh and spent catalysts indicates that Cu enhances the reducibility of Ni and suppresses both cracking reactions and coke-induced deactivation

Selective Targeting of Bromodomains of the Bromodomain-PHD Fingers Family Impairs Osteoclast Differentiation

Histone acetyltransferases of the MYST family are recruited to chromatin by BRPF scaffolding proteins. We explored functional consequences and the therapeutic potential of inhibitors targeting acetyl-lysine dependent protein interaction domains (bromodomains) present in BRPF1-3 in bone maintenance. We report three potent and selective inhibitors: one (PFI-4) with high selectivity for the BRPF1B isoform, and two pan-BRPF bromodomain inhibitors (OF-1, NI-57). The developed inhibitors displaced BRPF bromodomains from chromatin and did not inhibit cell growth and proliferation. Intriguingly, the inhibitors impaired RANKL-induced differentiation of primary murine bone marrow cells and human primary monocytes into bone resorbing osteoclasts by specifically repressing transcriptional programs required for osteoclastogenesis. The data suggest a key role of BRPF in regulating gene expression during osteoclastogenesis and the excellent druggability of these bromodomains may lead to new treatment strategies for patients suffering from bone loss or osteolytic malignant bone lesions