Search results for "TF"
showing 10 items of 1652 documents
Metformin influences drug sensitivity in pancreatic cancer cells
2018
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5–10% after diagnosis and treatment. Pancreatic cancer has been associated with type II diabetes as the frequency of recently diagnosed diabetics that develop pancreatic cancer within a 10-year period of initial diagnosis of diabetes in increased in comparison to non-diabetic patients. Metformin is a very frequently prescribed drug used to treat type II diabetes. Metformin acts in part by stimulating AMP-kinase (AMPK) and results in the suppression of mTORC1 activity and the induction o…
Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC
2019
Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date. We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA-sequencing data of the HNSCC TCGA dataset (N = 496) and a validation set (DKTK MASTER cohort, N = 10). Public single-cell gene expression data from 17 HPV-negative HNSCC were separately re-analyzed. APOBEC3-associated TCW motif mutations but not total single nucleotide variant burden were significantly associated with inflammation. This association was restricted to HPV-negative HNSCC samples. An APOBEC-enriched, HPV-nega…
Coronavirus Disease 2019–Associated Coagulopathy
2021
Patients with the severe form of coronavirus disease 2019 (COVID-19) have been frequently found to suffer from both arterial and venous thrombotic events due to the perpetuation of a hypercoagulable state. This phenomenon, termed COVID-19-associated coagulopathy (CC), is now considered a major component of the pathophysiology of this novel infectious disease, leading to widespread thrombosis. While at first, the vascular insults may be limited to the pulmonary microvasculature, as the disease progresses, systemic involvement occurs, culminating in distant organ thrombosis and multi-organ dysfunction syndrome. In this review article, we discuss recent insights into the pathophysiologic mecha…
Annual cycles of apoptosis, DNA strand breaks, heat shock proteins, and metallothionen isoforms in dab (Limanda limanda): influences of natural facto…
2013
The present study was undertaken to investigate the influence of natural and anthropogenic stressors on the induction of apoptosis, metallothionein (MT) isoforms, heat shock proteins and DNA strand breaks in the marine flatfish dab (Limbanda limanda) Seasonal changes and possible physiological influences were evaluated over a 1-year period at a fixed location northwest of Helgoland in the German Bight. These results were compared with data from sampling sites in the North Sea and the Baltic Sea. Annual cycles could be observed for all parameters except for Cd. The data revealed that changes in biomarker are not only linked to physiological processes related to reproduction but also to facto…
Dzieje organów w kościele parafialnym w Niemczy
2018
Pierwsze wzmianki o organach w kościele parafialnym w Niemczy pochodzą z przełomu XVI i XVII wieku. W latach 1597–1598 niewielki instrument wybudował Abraham Grasse. W 1617 roku ten sam organmistrz postawił nowe organy, liczące sześć głosów w manuale i trzy w pedale. Strawił je pożar w 1633 roku. W 1648 roku do odbudowanego kościoła zakupiono używany pozytyw. W 1725 roku świątynia wzbogaciła się o 20-głosowe organy wybudowane przez Ignatzego Mentzla. Służyły one parafii do 1852 roku, wówczas zamknięto, a następnie rozebrano kościół. Organy znajdujące się w obecnej świątyni pochodzą z 1866 roku i są dziełem Gottfrieda Riemera z Brzegu. Miały pierwotnie 18 głosów i mechaniczną trakturę rejest…
Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro ex…
2014
Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate. Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide) exhibiting negative food effect, and one highly-soluble and highly-permeable (metoprolol tartrate), serving as a negative control, were selected for the study. In vitro and in silico tools were used to evaluate the influence of media viscosity on drug bioperformance under fasted and fed conditions. The obtained results demonstrated that increased medium viscosity in the presence…
Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin
2021
Bariatric surgery is an effective treatment for severe obesity and related comorbidities, such as type II diabetes. Gastric bypass surgery shortens the length of the intestine, possibly leading to altered drug absorption. Metformin, a first-line treatment for type II diabetes, has permeability-dependent drug absorption, which may be sensitive to intestinal anatomic changes during bypass surgery, including Roux-en-Y gastric bypass (RYGB). Previous computer simulation data indicate increased metformin absorption after RYGB. In this study, we experimentally determined the region-dependent permeability of metformin, using the rat single-pass intestinal perfusion method (SPIP), which we then imp…
Do Cross-Country Differences in Accounting Conservatism Explain Variations in the Degree of Investor Diversification?
2009
We show that the level of conditional accounting conservatism of foreign markets is significantly and positively associated with decisions to diversify portfolios internationally. This positive association could be either because conditional conservatism per se is attractive to international investors, or because the un-modelled factors that attract foreign investors to a country also cause these countries to adopt conditionally conservative accounting practices. However, if conditional conservatism serves to alleviate foreign investors’ concerns related to insiders having asymmetric access to information then one would also expect the chosen mode of entry into a foreign market (as foreign …
Isoquercitrin and polyphosphate co-enhance mineralization of human osteoblast-like SaOS-2 cells via separate activation of two RUNX2 cofactors AFT6 a…
2014
Isoquercitrin, a dietary phytoestrogen, is a potential stimulator of bone mineralization used for prophylaxis of osteoporotic disorders. Here we studied the combined effects of isoquercitrin, a cell membrane permeable 3-O-glucoside of quercetin, and polyphosphate [polyP], a naturally occurring inorganic polymer inducing bone formation, on mineralization of human osteoblast-like SaOS-2 cells. Both compounds isoquercitrin and polyP induce at non-toxic concentrations the mineralization process of SaOS-2 cells. Co-incubation experiments revealed that isoquercitrin (at 0.1 and 0.3μM), if given simultaneously with polyP (as Ca(2+) salt; at 3, 10, 30 and 100μM) amplifies the mineralization-enhanci…
Wind-luminosity evolution in NLS1 AGN 1H 0707−495
2021
Ultra-fast outflows (UFOs) have been detected in the high-quality X-ray spectra of a number of active galactic nuclei (AGN) with fairly high accretion rates and are thought to significantly contribute to the AGN feedback. After a decade of dedicated study, their launching mechanisms and structure are still not well understood, but variability techniques may provide useful constraints. In this work, therefore, we perform a flux-resolved X-ray spectroscopy on a highly accreting and variable NLS1 AGN, 1H 0707-495, using all archival XMM-Newton observations to study the structure of the UFO. We find that the wind spectral lines weaken at higher luminosities, most likely due to an increasing ion…