Paving Luteolin Therapeutic Potentialities and Agro-Food-Pharma Applications: Emphasis on in Vivo Pharmacological Effects and Bioavailability Traits

Luteolin is a naturally occurring secondary metabolite belonging to the class of flavones. As many other natural flavonoids, it is often found in combination with glycosides in many fruits, vegetables, and plants, contributing to their biological and pharmacological value. Many preclinical studies report that luteolin present excellent antioxidant, anticancer, antimicrobial, neuroprotective, cardioprotective, antiviral, and anti-inflammatory effects, and as a consequence, various clinical trials have been designed to investigate the therapeutic potential of luteolin in humans. However, luteolin has a very limited bioavailability, which consequently affects its biological properties and efficacy. Several drug delivery strategies have been developed to raise its bioavailability, with nanoformulations and lipid carriers, such as liposomes, being the most intensively explored. Pharmacological potential of luteolin in various disorders has also been underlined, but to some of them, the exact mechanism is still poorly understood. Given the great potential of this natural antioxidant in health, this review is aimed at providing an extensive overview on the in vivo pharmacological action of luteolin and at stressing the main features related to its bioavailability, absorption, and metabolism, while essential steps determine its absolute health benefits and safety profiles. In addition, despite the scarcity of studies on luteolin bioavailability, the different drug delivery formulations developed to increase its bioavailability are also listed here.This study was partially supported by Çanakkale Onsekiz Mart Üniversitesi (Scientific Research Projects, ID: FYL-2017-1339 and FBA-2017-1268)

Paradigm of tunable clustering using binarization of consensus partition matrices (Bi-CoPaM) for gene discovery

Copyright @ 2013 Abu-Jamous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Clustering analysis has a growing role in the study of co-expressed genes for gene discovery. Conventional binary and fuzzy clustering do not embrace the biological reality that some genes may be irrelevant for a problem and not be assigned to a cluster, while other genes may participate in several biological functions and should simultaneously belong to multiple clusters. Also, these algorithms cannot generate tight clusters that focus on their cores or wide clusters that overlap and contain all possibly relevant genes. In this paper, a new clustering paradigm is proposed. In this paradigm, all three eventualities of a gene being exclusively assigned to a single cluster, being assigned to multiple clusters, and being not assigned to any cluster are possible. These possibilities are realised through the primary novelty of the introduction of tunable binarization techniques. Results from multiple clustering experiments are aggregated to generate one fuzzy consensus partition matrix (CoPaM), which is then binarized to obtain the final binary partitions. This is referred to as Binarization of Consensus Partition Matrices (Bi-CoPaM). The method has been tested with a set of synthetic datasets and a set of five real yeast cell-cycle datasets. The results demonstrate its validity in generating relevant tight, wide, and complementary clusters that can meet requirements of different gene discovery studies.National Institute for Health Researc

Calibration of the Milagro Cosmic Ray Telescope

The Milagro detector is an air shower array which uses the water Cherenkov technique and is capable of continuously monitoring the sky at energies near 1 TeV. The detector consists of 20000 metric tons of pure water instrumented with 723 photo-multiplier tubes (PMTs). The PMTs are arranged in a two-layer structure on a lattice of 3 m spacing covering 5000 $m^2$ area. The direction of the shower is determined from the relative timing of the PMT signals, necessitating a common time reference and amplitude slewing corrections to improve the time resolution. The calibration system to provide these consists of a pulsed laser driving 30 diffusing light sources deployed in the pond to allow cross-calibration of the PMTs. The system is capable of calibrating times and the pulse-heights from the PMTs using the time-over-threshold technique. The absolute energy scale is provided using single muons passing through the detector. The description of the calibration system of the Milagro detector and its prototype Milagrito will be presented.Comment: 4 pages, submitted to the XXVI International Cosmic Ray Conferenc

Search for Short Duration Bursts of TeV Gamma Rays with the Milagrito Telescope

The Milagrito water Cherenkov telescope operated for over a year. The most probable gamma-ray energy was ~1 TeV and the trigger rate was as high as 400 Hz. We have developed an efficient technique for searching the entire sky for short duration bursts of TeV photons. Such bursts may result from "traditional" gamma-ray bursts that were not in the field-of-view of any other instruments, the evaporation of primordial black holes, or some as yet undiscovered phenomenon. We have begun to search the Milagrito data set for bursts of duration 10 seconds. Here we will present the technique and the expected results. Final results will be presented at the conference.Comment: submitted to XXVI International Cosmic Ray Conference, Salt Lake Cit

Instrumented Water Tanks can Improve Air Shower Detector Sensitivity

Previous works have shown that water Cherenkov detectors have superior sensitivity to those of scintillation counters as applied to detecting extensive air showers (EAS). This is in large part due to their much higher sensitivity to EAS photons which are more than five times more numerous than EAS electrons. Large area water Cherenkov detectors can be constructed relatively cheaply and operated reliably. A sparse detector array has been designed which uses these types of detectors to substantially increase the area over which the Milagro Gamma Ray Observatory collects EAS information. Improvements to the Milagro detector's performance characteristics and sensitivity derived from this array and preliminary results from a prototype array currently installed near the Milagro detector will be presented.Comment: 4 pages, submitted to XXVI International Cosmic Ray Conference, Salt Lake Cit

Study of the Shadows of the Moon and the Sun with VHE Cosmic Rays

Milagrito, a prototype for the Milagro detector, operated for 15 months in 1997-8 and collected 8.9 billion events. It was the first extensive air shower (EAS) array sensitive to showers intiated by primaries with energy below 1 TeV. The shadows of the sun and moon observed with cosmic rays can be used to study systematic pointing shifts and measure the angular resolution of EAS arrays. Below a few TeV, the paths of cosmic rays coming toward the earth are bent by the helio- and geo-magnetic fields. This is expected to distort and displace the shadows of the sun and the moon. The moon shadow, offset from the nominal (undeflected) position, has been observed with high statistical significance in Milagrito. This can be used to establish energy calibrations, as well as to search for the anti-matter content of the VHE cosmic ray flux. The shadow of the sun has also been observed with high significance.Comment: 4 pages, submitted to XXVI International Cosmic Ray Conference, Salt Lake Cit

The high-energy gamma-ray fluence and energy spectrum of GRB 970417a from observations with Milagrito

Evidence of TeV emission from GRB970417a has been previously reported using data from the Milagrito detector. Constraints on the TeV fluence and the energy spectrum are now derived using additional data from a scaler system that recorded the rate of signals from the Milagrito photomultipliers. This analysis shows that if emission from GRB970417a has been observed, it must contain photons with energies above 650 GeV. Some consequences of this observation are discussed.Comment: Submitted to the Astrophysical Journa