133 research outputs found
A new life for sterile neutrino dark matter after the pandemic
We propose a novel mechanism to generate sterile neutrinos in theearly Universe, by converting ordinary neutrinos in scatteringprocesses . After initial production byoscillations, this leads to an exponential growth in the abundance. Weshow that such a production regime naturally occurs for self-interacting, and that this opens up significant new parameter space where make up all of the observed dark matter. Our results provide strong motivationto further push the sensitivity of X-ray line searches, and to improve onconstraints from structure formation.<br
A new life for sterile neutrino dark matter after the pandemic
We propose a novel mechanism to generate sterile neutrinos in the early Universe, by converting ordinary neutrinos in scattering processes . After initial production by oscillations, this leads to an exponential growth in the abundance. We show that such a production regime naturally occurs for self-interacting , and that this opens up significant new parameter space where make up all of the observed dark matter. Our results provide strong motivation to further push the sensitivity of X-ray line searches, and to improve on constraints from structure formation
A new life for sterile neutrino dark matter after the pandemic
We propose a novel mechanism to generate sterile neutrinos in theearly Universe, by converting ordinary neutrinos in scatteringprocesses . After initial production byoscillations, this leads to an exponential growth in the abundance. Weshow that such a production regime naturally occurs for self-interacting, and that this opens up significant new parameter space where make up all of the observed dark matter. Our results provide strong motivationto further push the sensitivity of X-ray line searches, and to improve onconstraints from structure formation.<br
Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions
Misregulation and mutations of the transcription factor Nrf2 are involved in the development of a variety of human diseases. In this study, we employed the technology of stapled peptides to address a protein-DNA-complex and designed a set of Nrf2-based derivatives. Varying the length and position of the hydrocarbon staple, we chose the best peptide for further evaluation in both fixed and living cells. Peptide 4 revealed significant enrichment within the nucleus compared to its linear counterpart 5, indicating potent binding to DNA. Our studies suggest that these molecules offer an interesting strategy to target activated Nrf2 in cancer cells
Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions
Misregulation and mutations of the transcription factor Nrf2 are involved in the development of a variety of human diseases. In this study, we employed the technology of stapled peptides to address a protein-DNA-complex and designed a set of Nrf2-based derivatives. Varying the length and position of the hydrocarbon staple, we chose the best peptide for further evaluation in both fixed and living cells. Peptide 4 revealed significant enrichment within the nucleus compared to its linear counterpart 5, indicating potent binding to DNA. Our studies suggest that these molecules offer an interesting strategy to target activated Nrf2 in cancer cells
Association of lower fractional flow reserve values with higher risk of adverse cardiac events for lesions deferred revascularization among patients with acute coronary syndrome
BACKGROUND: The safety of deferring revascularization based on fractional flow reserve (FFR) during acute coronary syndrome (ACS) is unclear. We evaluated the association of FFR and adverse cardiac events among patients with coronary lesions deferred revascularization based on FFR in the setting of ACS versus non-ACS. METHODS AND RESULTS: The study population (674 patients; 816 lesions) was divided into ACS (n=334) and non-ACS (n=340) groups based on the diagnosis when revascularization was deferred based on FFR values >0.80 between October 2002 and July 2010. The association and interaction between FFR and clinical outcomes was evaluated using Cox proportional hazards models within each group (mean follow-up of 4.5Β±2.1Β years). Subsequent revascularization of a deferred lesion was classified as a deferred lesion intervention (DLI), whereas the composite of DLI or myocardial infarction (MI) attributed to a deferred lesion was designated as deferred lesion failure (DLF). In the non-ACS group, lower FFR values were not associated with any increase in adverse cardiac events. In the ACS group, every 0.01 decrease in FFR was associated with a significantly higher rate of cardiovascular death, MI, or DLI (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03 to 1.12), MI or DLI (HR, 1.09; 95% CI: 1.04 to 1.14), DLF (HR, 1.12; 95% CI, 1.06 to 1.18), MI (HR, 1.07; 95% CI, 1.00 to 1.14), and DLI (HR, 1.12; 95% CI, 1.06 to 1.18). CONCLUSION: Lower FFR values among ACS patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events. This association was not observed in non-ACS patients
Cellular model system to dissect the isoform-selectivity of Akt inhibitors
The protein kinase Akt plays a pivotal role in cellular processes. However, its isoformsβ distinct functions have not been resolved to date, mainly due to the lack of suitable biochemical and cellular tools. Against this background, we present the development of an isoform-dependent Ba/F3 model system to translate biochemical results on isoform specificity to the cellular level. Our cellular model system complemented by protein X-ray crystallography and structure-based ligand design results in covalent-allosteric Akt inhibitors with unique selectivity profiles. In a first proof-of-concept, the developed molecules allow studies on isoform-selective effects of Akt inhibition in cancer cells. Thus, this study will pave the way to resolve isoform-selective roles in health and disease and foster the development of next-generation therapeutics with superior on-target properties
ΠΠ±ΡΠ΅ΠΌΠ½Π°Ρ ΠΊΠ°ΠΏΠ½ΠΎΠ³ΡΠ°ΡΠΈΡ ΠΊΠ°ΠΊ ΡΠΏΠΎΡΠΎΠ± ΠΎΡΠ΅Π½ΠΊΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π°Π»ΡΠ²Π΅ΠΎΠ»ΡΡΠ½ΠΎΠΉ Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΠΈ Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠ΅
The purpose of the study was to compare the relationship between the dead space volume and tidal volume (VD/VT) using volumetric capnography (VCap) during pressure controlled (PCV) and pressure supported (PSV) ventilation mode in the postoperative period.Materials and methods. 30 randomly assigned cardiac surgical patients undergoing CABG (coronary artery bypass grafting) using ECC (extracorporeal circuit) were included in an observational, prospective study. Patients were connected to the ventilator immediately after ICU admission. After that, monitoring VD/VT, CO2 production (VECO2) as well as ventilation parameters was carried out. The parameters during PCV and PSV mode were statistically evaluated using t-test.Results. Expiratory CO2 (ETCO2) concentration were not significantly different in both PCV or PSV (p=NS), although both VECO2 and minute ventilation (MV) increased during PSV mode (p<0.01). VD/VT in PSV mode was lower than in PCV. Gas exchange represented by alveolar ventilation (VA) was better during PSV (p<0.01). VA was also higher during PSV (p<0.05). The calculated VD/VT ratio differed between PCV and PSV mode (p<0.01).Conclusion. VCap represents a tool for monitoring of CO2 exchange effectivness. We registered a decrease in VD/VT with improved alveolar ventilation (VA) in PSV mode. VCap seems to be a suitable instrument for adjustment of protective lung ventilation.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΡΡΠ°Π²Π½ΠΈΡΡ Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·Ρ ΠΌΠ΅ΠΆΠ΄Ρ ΠΎΠ±ΡΠ΅ΠΌΠΎΠΌ ΠΌΠ΅ΡΡΠ²ΠΎΠ³ΠΎ ΠΏΡΠΎΡΡΡΠ°Π½ΡΡΠ²Π° ΠΈ Π΄ΡΡ
Π°ΡΠ΅Π»ΡΠ½ΡΠΌ ΠΎΠ±ΡΠ΅ΠΌΠΎΠΌ (VD/VT) ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΎΠ±ΡΠ΅ΠΌΠ½ΠΎΠΉ ΠΊΠ°ΠΏΠ½ΠΎΠ³ΡΠ°ΡΠΈΠΈ (VCap) Π² ΡΠ΅ΠΆΠΈΠΌΠ°Ρ
ΠΈΡΠΊΡΡΡΡΠ²Π΅Π½Π½ΠΎΠΉ Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΠΈ Π»Π΅Π³ΠΊΠΈΡ
Ρ ΡΠΏΡΠ°Π²Π»ΡΠ΅ΠΌΡΠΌ Π΄Π°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ (PCV) ΠΈ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΠΎΠΉ Π΄Π°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ (PSV) Π² ΠΏΠΎΡΠ»Π΅ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΌ ΠΏΠ΅ΡΠΈΠΎΠ΄Π΅.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π ΠΎΠ±ΡΠ΅ΡΠ²Π°ΡΠΈΠΎΠ½Π½ΠΎΠ΅, ΠΏΡΠΎΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ»ΡΡΠ°ΠΉΠ½ΠΎΠ³ΠΎ Π²ΡΠ±ΠΎΡΠ° Π²ΠΊΠ»ΡΡΠΈΠ»ΠΈ 30 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΈΠ· ΠΎΡΠ΄Π΅Π»Π΅Π½ΠΈΡ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎ-ΡΠΎΡΡΠ΄ΠΈΡΡΠΎΠΉ Ρ
ΠΈΡΡΡΠ³ΠΈΠΈ, ΠΏΠ΅ΡΠ΅Π½Π΅ΡΡΠΈΡ
ΠΎΠΏΠ΅ΡΠ°ΡΠΈΡ Π°ΠΎΡΡΠΎΠΊΠΎΡΠΎΠ½Π°ΡΠ½ΠΎΠ³ΠΎ ΡΡΠ½ΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ (ΠΠΠ¨) Ρ ΡΠΊΡΡΡΠ°ΠΊΠΎΡΠΏΠΎΡΠ°Π»ΡΠ½ΡΠΌ ΠΊΡΠΎΠ²ΠΎΠΎΠ±ΡΠ°ΡΠ΅Π½ΠΈΠ΅ΠΌ. ΠΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΏΠΎΠ΄ΠΊΠ»ΡΡΠ°Π»ΠΈ ΠΊ ΡΠΈΡΡΠ΅ΠΌΠ΅ Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΠΈ Π»Π΅Π³ΠΊΠΈΡ
ΡΡΠ°Π·Ρ ΠΏΡΠΈ ΠΏΠΎΡΡΡΠΏΠ»Π΅Π½ΠΈΠΈ Π² ΠΎΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ. ΠΠ°ΡΠ΅ΠΌ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³ VD/VT, ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠΈ CO2 (VECO2), Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠΎΠ² Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΠΈ. ΠΠ°ΡΠ°ΠΌΠ΅ΡΡΡ Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΠΈ Π² ΡΠ΅ΠΆΠΈΠΌΠ°Ρ
Ρ ΡΠΏΡΠ°Π²Π»ΡΠ΅ΠΌΡΠΌ Π΄Π°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ (PCV) ΠΈ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΠΎΠΉ Π΄Π°Π²Π»Π΅Π½ΠΈΠ΅ΠΌ (PSV) ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ ΠΎΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈΠ Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠ΅ Π²ΡΡΠ²ΠΈΠ»ΠΈ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΡΡ
ΡΠ°Π·Π»ΠΈΡΠΈΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ CO2 Π²ΠΎ Π²ΡΠ΄ΡΡ
Π°Π΅ΠΌΠΎΠΌ Π²ΠΎΠ·Π΄ΡΡ
Π΅ (ETCO2) ΠΌΠ΅ΠΆΠ΄Ρ ΡΠ΅ΠΆΠΈΠΌΠ°ΠΌΠΈ PCV ΠΈ PSV (p=NS), Ρ
ΠΎΡΡ ΠΊΠ°ΠΊ VECO2, ΡΠ°ΠΊ ΠΈ ΠΌΠΈΠ½ΡΡΠ½Π°Ρ Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΡ (MV) Π²ΠΎΠ·ΡΠ°ΡΡΠ°Π»ΠΈ Π² ΡΠ΅ΠΆΠΈΠΌΠ΅ PSV (p<0,01). ΠΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ VD/VT Π² ΡΠ΅ΠΆΠΈΠΌΠ΅ PSV Π±ΡΠ»ΠΎ Π½ΠΈΠΆΠ΅, ΡΠ΅ΠΌ Π² ΡΠ΅ΠΆΠΈΠΌΠ΅ PCV. ΠΠ°Π·ΠΎΠΎΠ±ΠΌΠ΅Π½, ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΡΠΉ Π°Π»ΡΠ²Π΅ΠΎΠ»ΡΡΠ½ΠΎΠΉ Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΠ΅ΠΉ (VA), Π±ΡΠ» Π»ΡΡΡΠ΅ Π² ΡΠ΅ΠΆΠΈΠΌΠ΅ PSV (p<0,01). ΠΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Ρ VA Π±ΡΠ» ΡΠ°ΠΊΠΆΠ΅ Π²ΡΡΠ΅ Π² ΡΠ΅ΠΆΠΈΠΌΠ΅ PSV (p<0,05). Π Π°ΡΡΠ΅ΡΠ½ΠΎΠ΅ ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ VD/VT ΡΠ°Π·Π»ΠΈΡΠ°Π»ΠΎΡΡ ΠΌΠ΅ΠΆΠ΄Ρ ΡΠ΅ΠΆΠΈΠΌΠ°ΠΌΠΈ PCV ΠΈ PSV (p<0,01).ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ±ΡΠ΅ΠΌΠ½Π°Ρ ΠΊΠ°ΠΏΠ½ΠΎΠ³ΡΠ°ΡΠΈΡ (VCap) ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³Π° ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΎΠ±ΠΌΠ΅Π½Π° CO2. ΠΡΠΌΠ΅ΡΠ°Π»ΠΈ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ VD/VT Ρ ΡΠ»ΡΡΡΠ΅Π½ΠΈΠ΅ΠΌ Π°Π»ΡΠ²Π΅ΠΎΠ»ΡΡΠ½ΠΎΠΉ Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΠΈ (VA) Π² ΡΠ΅ΠΆΠΈΠΌΠ΅ PSV. VCap ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΡΡΠΈΠΌ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ΅Π³ΡΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΠΈ Π»Π΅Π³ΠΊΠΈΡ
Clinical outcomes of deferred revascularisation using fractional flow reserve in patients with and without diabetes mellitus
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