Preparation and characterization of a tumor-targeting dual-image system based on iron oxide nanoparticles functionalized with folic acid and rhodamine

Cancer is one of the diseases with most deaths worldwide, around 8.2 million annually. For this reason, several treatments and diagnostic tools have been investigated and developed over the past decades. Among them, a dual-image system has been developed to achieve and enhance the detection of cancer, which has not been done with systems currently available. The present study describes the preparation of a dual-image targeting system composed of magnetic iron oxide nanoparticles functionalized with folic acid and rhodamine; nanoparticles synthesis was achieved by a coprecipitation method; the functionalization was carried out by a carbodiimide with folic acid and/or the rhodamine isothiocyanate; conjugates were characterized by spectrometric techniques; toxicity was measured by cell proliferation assay on HeLa cells using progressive concentrations of functionalized nanoparticles. Cellular uptake assay was carried out by competitive assay on HeLa cells. Iron oxide magnetite nanoparticles, modified with folic acid and rhodamine, were successfully synthetized with a particle size lower than 20nm (TEM), EDS, HRTEM, and XDR showed highly crystalline Fe3O4 nanoparticles. Folic acid and rhodamine were conjugated with high efficiency. A significant selectivity and uptake, facilitated by surface modification of iron oxide nanoparticles with folic acid, were demonstrated.The multifunctional system showed suitable physicochemical and biological properties for cell targeting through folate receptors.This study was supported by the International Atomic Energy Agency (CRP-F22064, Contract no. 18358) and the Universidad Autónoma del Estado de México, through Project no. 3543/2013CHT

Risk-aware Adaptive Virtual CPU Oversubscription in Microsoft Cloud via Prototypical Human-in-the-loop Imitation Learning

Oversubscription is a prevalent practice in cloud services where the system offers more virtual resources, such as virtual cores in virtual machines, to users or applications than its available physical capacity for reducing revenue loss due to unused/redundant capacity. While oversubscription can potentially lead to significant enhancement in efficient resource utilization, the caveat is that it comes with the risks of overloading and introducing jitter at the level of physical nodes if all the co-located virtual machines have high utilization. Thus suitable oversubscription policies which maximize utilization while mitigating risks are paramount for cost-effective seamless cloud experiences. Most cloud platforms presently rely on static heuristics-driven decisions about oversubscription activation and limits, which either leads to overloading or stranded resources. Designing an intelligent oversubscription policy that can adapt to resource utilization patterns and jointly optimizes benefits and risks is, largely, an unsolved problem. We address this challenge with our proposed novel HuMan-in-the-loop Protoypical Imitation Learning (ProtoHAIL) framework that exploits approximate symmetries in utilization patterns to learn suitable policies. Also, our human-in-the-loop (knowledge-infused) training allows for learning safer policies that are robust to noise and sparsity. Our empirical investigations on real data show orders of magnitude reduction in risk and significant increase in benefits (saving stranded cores) in Microsoft cloud platform for 1st party (internal services).Comment: 9 pages, 3 figure

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

A Lightweight Framework for Exchanging Web Data

We propose a lightweight framework for data exchange that is suitable for non-expert and casual users sharing data on theWeb and/or through peer-to-peer systems. Unlike previ- ous work, we consider a minimalistic data model and schema formalism that are suitable for describing online data and propose algorithms for mapping such schemas as well as for translating the corresponding instances. Also our solution requires minimal overhead and setup costs (e.g., we consider data stored in tables, XML or CSV files) comparing to ex- isting data exchange systems, making it very attractive in our setting. We report experimental results indicating that our method works well with real Web data from various do- mains.We are currently acquiring citations for the work deposited into this collection. We recognize the distribution rights of this item may have been assigned to another entity, other than the author(s) of the work.If you can provide the citation for this work or you think you own the distribution rights to this work please contact the Institutional Repository Administrator at [email protected]

Ciência Brasil - the brazilian portal of science and technology

Research social networks are a potentially useful resource for studying science and technology indicators from specific communities (e.g., acountry). However, building and analyzing such networks beget challenges beyond those from regular social networks, since data about actors and their relationships are usually dispersed across various sources. In this paper, we present a research social network built from an individual perspective by gathering data from a Brazilian curricula vitae repository. We describe its architecture and the solutions adopted for data collection, extraction and deduplication, and for materializing and visualizing the network