Search results for "target"
showing 10 items of 1196 documents
HOW SMART DOES AN AGENT NEED TO BE?
2005
The classic distributed computation is done by atoms, molecules or spins in vast numbers, each equipped with nothing more than the knowledge of their immediate neighborhood and the rules of statistical mechanics. These agents, 1023 or more, are able to form liquids and solids from gases, realize extremely complex ordered states, such as liquid crystals, and even decode encrypted messages. We will describe a study done for a sensor-array "challenge problem" in which we have based our approach on old-fashioned simulated annealing to accomplish target acquisition and tracking under the rules of statistical mechanics. We believe the many additional constraints that occur in the real problem ca…
No evidence for sequences structurally related to the RB1 gene in the human genome.
1991
The retinoblastoma (RB1) gene is a ubiquitously expressed gene encoding a cell-cycle control protein. Inactivation of this gene plays a crucial role in the development of retinoblastoma, osteosarcoma, and other tumors. In a search for structurally related gene sequences we identified a 5.5-kb BamHI fragment strongly cross-hybridizing with the 5′ end of the RB1 cDNA. Molecular cloning, in situ hybridization, restriction mapping, and sequence analysis identified this DNA segment as the 28S rRNA gene. The absence of other cross-hybridizing sequences suggests that the RB1 gene is not part of a structurally related gene family.
Characterization of Hydrophilic Gold(I) N-Heterocyclic Carbene (NHC) Complexes as Potent TrxR Inhibitors Using Biochemical and Mass Spectrometric App…
2017
We report here on the synthesis of a series of mono-and dinuclear gold(I) complexes exhibiting sulfonated bis(NHC) ligands and novel hydroxylated mono(NHC) Au(I) compounds, which were also examined for their 'biological activities. Initial cell viability assays show strong antiproliferative activities of the hydroxylated mono(NHC) gold compounds (8 > 9 > 10) against 2008 human ovarian cancer cells even after 1 h incubation. In order to gain insight into the mechanism of biological action of the gold compounds, their effect on the pivotal cellular target seleno-enzyme thioredoxin reductase (TrxR), involved in the maintenance of intracellular redox balance, was investigated in depth. Th…
New Gold(I) Organometallic Compounds with Biological Activity in Cancer Cells
2014
N-Heterocyclic carbene gold(I) complexes bearing a fluorescent coumarin ligand were synthesized and characterized by various techniques. The compounds were examined for their antiproliferative effects in normal and tumor cells in vitro; they demonstrated moderate activity and a certain degree of selectivity. The compounds were also shown to efficiently inhibit the selenoenzyme thioredoxin reductase (TrxR), whereas they were poorly effective towards the glutathione reductase (GR) and glutathione peroxidase enzymes. Notably, {3-[(7-methoxy-2-oxo-2H-chromen-4-yl) methyl]-1-methylimidazol-2-ylidene}(tetra-O-acetyl-1-thio-beta-D-glucopyranosido) gold(I) (3) showed a pronounced inhibition of TrxR…
A critical evaluation of caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura
2020
Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy caused by inhibitory autoantibodies against ADAMTS13 protein. Until recently, the combination of plasma exchange (PEX) and immunosuppression has been the standard front-line treatment in this disorder. However, aTTP-related mortality, refractoriness, and relapse are still a matter of concern. Areas covered: The better understanding of the pathophysiological mechanisms of aTTP has allowed substantial improvements in the diagnosis and treatment of this disease. Recently, the novel anti-VWF nanobody caplacizumab has been approved for acute episodes of aTTP. Caplacizumab is capable to block the adh…
SYNTHESIS, CHARACTERIZATION AND IN VITRO CYTOTOXICITY STUDIES OF A MACROMOLECULAR CONJUGATE OF PACLITAXEL BEARING OXYTOCIN AS TARGETING MOIETY.
2007
The present study describes the experimental synthetic procedure and the characterization of a new polyaspartamide macromolecular prodrug of paclitaxel, bearing oxytocin residues as targeting moieties. In vitro stability studies of bioconjugate, performed in media mimicking biological fluids (buffer solutions at pH 7.4 and 5.5) and in human plasma, evidenced the high stability of the targeting portion (oxytocin)-polymer linkage and the ability of this conjugate to release linked paclitaxel in a prolonged way in plasma. Moreover, preliminary in vitro antiproliferative studies, carried out on MCF-7 cells, that are oxytocin receptor positive cells, showed that the polymeric conjugate has the s…
In human endothelial cells rapamycin causes mTORC2 inhibition and impairs cell viability and function.
2008
Aim Drug-eluting stents are widely used to prevent restenosis but are associated with late endothelial damage. To understand the basis for this effect, we have studied the consequences of a prolonged incubation with rapamycin on the viability and functions of endothelial cells. Methods and results Human umbilical vein or aorta endothelial cells were exposed to rapamycin in the absence or in the presence of tumour necrosis factor α (TNFα). After a 24 h-incubation, rapamycin (100 nM) caused a significant cell loss associated with the increase of both apoptosis and necrosis, as quantified by propidium iodide staining, caspase 3 activity, and lactate dehydrogenase release. Rapamycin also impair…
Risk Burden of Coronary Perforation in Chronic Total Occlusion Recanalization: Latin American CTO Registry Analysis
2022
Background Coronary perforation is a life‐threatening complication of acute percutaneous coronary intervention (PCI) for chronic total occlusions (CTO), but data on midterm outcomes are limited. Methods and Results Data from LATAM (Latin American)‐CTO Registry (57 centers; 9 countries) were analyzed. We assessed the risk of 30‐day, 1‐year major adverse cardiac events of coronary perforation using time‐to‐event and weighted composite end point analysis having CTO PCI without perforation as comparators. Additionally, we studied the independent predictors of perforation in these patients. Of 2054 patients who underwent CTO PCI between 2015 and 2018, the median Multicenter CTO Registry in Japa…
Chloroplast signal length requirement reflects the outer membrane and TOC complex dimension
2015
Background and Purpose: The evolution of an efficient preprotein targeting and translocation system was a central prerequisite for the endosymbiotic integration of a -proteobacteria and cyanobacteria as cellular organelles. Today, it is widely accepted that during evolution most (pre-)proteins destined for these two organelles were equipped with an N-terminal targeting signal for localization. While multiple modes of evolution of these extensions are currently discussed, all evolved signals serve the same function – forming a signal for targeting to the correct organelle and translocation across both membranes. We aimed to generalize the current idea for the length requirement of the N-term…
Intercultural Aspects of Specialized Translation The Language of Traditional Chinese Medicine in a Globalized Context
2022
Traditional Chinese Medicine (TCM) has a very ancient history and its importance for human health has long been acknowledged worldwide. The significant role that TCM plays in the global healthcare system has been officially recognized by the World Health Organization (WHO), which devoted a chapter to TCM in the 2019 latest version of the International Classification of Diseases and Related Health Problems (ICD-11). TCM, alone or in combination with Western Medicine (WM), has been recommended for various health conditions (Aung et al., 2013; Cai et al., 2015; Zhang et al., 2015) – including mild COVID-19-related symptoms (Zhao et al. 2021). As a result of globalization, which has fostered th…