BACKGROUND: Small molecule inhibitors of phosphatidylinositol-3 kinase (PI3K) have been developed as molecular therapy for cancer, but their efficacy in the clinic is modest, hampered by resistance mechanisms.METHODS: We studied the effect of PI3K therapy in patient-derived tumor organotypic cultures (from five patient samples), three glioblastoma (GBM) tumor cell lines, and an intracranial model

Inflammatory mediators present in the tumor milieu may promote cancer progression and are considered promising targets of novel biological therapies. We previously reported that the marine antitumor agent trabectedin, approved in Europe in 2007 for soft tissue sarcomas and in 2009 for ovarian cancer, was able to downmodulate the production of selected cytokines/chemokines in immune cells. Patients

The p73 locus gene has a complex structure encoding a plethora of isoforms. The different DeltaN truncated isoforms of p73 may exert different activities depending on the cellular context. The beta isoform of DeltaNp73 seems to have a particular pattern of action even if its role in cell cycle and mitosis is still under investigation. To gain further knowledge of DeltaNp73beta's function, we inves

The Ukrainian shield hosts two Palaeoproterozoic anorthosite-mangerite-charnockite-granite (AMCG) complexes (the Korosten and Korsun-Novomyrhorod complexes) that intruded Palaeoproterozoic continental crust in north-western and central parts of the shield, respectively. We report results of U-Pb zircon and baddeleyite dating of 16 samples from the Korosten plutonic complex (KPC), and 6 samples fro

This article reports an analysis of the first detailed chemistry direct numerical simulation (DNS) of a high Karlovitz number laboratory premixed flame. The DNS results are first compared with those from laser-based diagnostics with good agreement. The subsequent analysis focuses on a detailed investigation of the flame area, its local thickness and their rates of change in isosurface following re

Introduction Healthcare databases are useful sources to investigate the epidemiology of chronic obstructive pulmonary disease (COPD), to assess longitudinal outcomes in patients with COPD, and to develop disease management strategies. However, in order to constitute a reliable source for research, healthcare databases need to be validated. The aim of this protocol is to perform the first systemati

The number of patients affected by Alzheimer's disease among the population is currently growing, while the availability of resources for their assistance is decreasing. A solution for this problem is provided by the use of Ambient Assisted Living technologies, with the objectives to prolong the independent living of patients at home, to relieve assistance burden on caregivers, and to improve care

Objectives: The paper describes recruitment results and characteristics of the UP-TECH clinical trial sample, including level of care services use, informal caregiver burden and its determinants.Methods: UP-TECH is designed to test innovative care solutions for community-dwelling patients with moderate stage Alzheimer's disease and their caregivers in Italy. Four hundred and fifty patient-caregive

Chondroadherin (CHAD) is a cartilage matrix protein that mediates the adhesion of isolated chondrocytes. Its protein core is composed of 11 leucine-rich repeats (LRR) flanked by cysteine-rich domains. CHAD makes important interactions with collagen as well as with cell-surface heparin sulfate proteoglycans and α2β1 integrins. The integrin-binding site is located in a region of hitherto unknown str

Cyclometallation of 8-methylquinoline and 2-(dimethylamino)-pyridine in an iridium-based pincer complex is described. The C−H activation of 2-(dimethylamino)pyridine is not chelation assisted, which has not been described before for Csp3−H bonds in cyclometallation reactions. The mechanism of the cyclometallation of 2-(dimethylamino)pyridine was studied by DFT calculations and kinetic measurements

The proper alignment of requirements engineering and testing (RET) can be key to software's success. Three practices can provide effective RET alignment: using test cases as requirements, harvesting trace links, and reducing distances between requirements engineers and testers. The Web extra https://youtu.be/M65ZKxfxqME is an audio podcast of author Elizabeth Bjarnason reading the the Requirements

Gene transfer is a promising drug delivery method of advanced therapeutic entities for Parkinson's disease. One advantage over conventional therapies, such as peripheral delivery of the dopamine pre-cursor L-DOPA, is site-specific expression of proteins with regenerative, disease-modifying and potentially neuroprotective capacity. Several clinical trials have been performed to test the capacity of

This study deals with the diffusion of a new medical technology — vaccination against smallpox — in nineteenth-century Scania in Sweden. Using an aggregated sample of parishes as well as a micro-level dataset for four parishes, we investigate the socioeconomic as well as the geographical patterns of diffusion of vaccination in the province. We also relate the adoption of vaccination across geograp

Obesity and its associated comorbidities (for example, diabetes mellitus and hepatic steatosis) contribute to approximately 2.5 million deaths annually and are among the most prevalent and challenging conditions confronting the medical profession. Neurotensin (NT; also known as NTS), a 13-amino-acid peptide predominantly localized in specialized enteroendocrine cells of the small intestine and rel