Thymosin β4 is differentially expressed in the cerebrospinal fluid of Creutzfeldt‐Jakob disease patients: a MALDI‐TOF MS protein profiling study

MALDI‐TOF protein profiling analysis permits the detection of peptides and small proteins in complex protein mixtures with great accuracy. We applied this analysis to cerebrospinal fluid (CSF) from 15 patients affected by Creutzfeldt‐Jakob disease (CJD). We compared the levels of the normalized ion signals of 11 sporadic and 4 genetic CJD forms with those from ten healthy control subjects and eight non‐CJD relapsing‐remitting multiple sclerosis patients. In so doing, we detected 61 differentially expressed ion signals in CJD samples compared to controls. Among the 61 signals, 3 signals had significantly increased levels with high statistical significance (p <0.0001) and were located at 3238.3 m/z, 4963.7 m/z, and 8565.3 m/z. We characterized the 5.0 and 8.6 kDa proteins as thymosin β4 N‐acetylated and free ubiquitin, respectively, while the 3.2‐kDa peptide remained uncharacterized. Although elevated ubiquitin levels have previously been described in CJD, we have demonstrated for the first time the involvement of thymosin β4 in a neurodegenerative disease. To support the validity of thymosin β4 levels obtained by MALDI‐TOF analysis, an independent enzyme immunoassay analysis was performed. Moreover, a validation cohort consisting of CSF from three CJD patients, five healthy subjects, and six non‐CJD relapsing‐remitting multiple sclerosis patients was analyzed in a similar way, yielding superimposable results. We propose that thymosin β4 is a potential new candidate marker for the ante mortem diagnosis of CJD disease.     

Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.     

Prediction of geometric uncertainty effects on Fluid Dynamics by Polynomial Chaos and Fictitious Domain method

In this paper the Tensorial-expanded Chaos Collocation method has been used to solve Fluid Dynamic problems with geometric uncertainties. The main advantage of the Tensorial-expanded Chaos Collocation method is its non-intrusive formulation, so existing deterministic solvers can be used. A Least-Squares Spectral Element Method has been employed for the analysis of the deterministic differential problems obtained by Tensorial-expanded Chaos Collocation. This algorithm exploits a Fictitious Domain approach, so it is particularly suitable to solve differential problems defined on stochastic domains. The great capabilities of the Tensorial-expanded Chaos Collocation method combined to the Fictitious Domain-Least-Squares Spectral Element Method are demonstrated by numerical experiments.     

Atom-Aid: Detecting and Surviving Atomicity Violations

Hardware can play a significant role in improving reliability of multithreaded software. Recent architectural proposals arbitrarily group consecutive dynamic memory operations into atomic blocks to enforce coarse-grained memory ordering, providing implicit atomicity. The authors of this article observe that implicit atomicity probabilistically hides atomicity violations by reducing the number of interleaving opportunities between memory operations. They propose Atom-Aid, which creates implicit atomic blocks intelligently instead of arbitrarily, dramatically reducing the probability that atomicity violations will manifest themselves.     

An experimental study on the applicability of evolutionary algorithms to craniofacial superimposition in forensic identification

Photographic supra-projection is a forensic process that aims to identify a missing person from a photograph and a skull found. One of the crucial tasks throughout all this process is the craniofacial superimposition which tries to find a good fit between a 3D model of the skull and the 2D photo of the face. This photographic supra-projection stage is usually carried out manually by forensic anthropologists. It is thus very time consuming and presents several difficulties. In this paper, we aim to demonstrate that real-coded evolutionary algorithms are suitable approaches to tackle craniofacial superimposition. To do so, we first formulate this complex task in forensic identification as a numerical optimization problem. Then, we adapt three different evolutionary algorithms to solve it: two variants of a real-coded genetic algorithm and the state of the art evolution strategy CMA-ES. We also consider an existing binary-coded genetic algorithm as a baseline. Results on several superimposition problems of real-world identification cases solved by the Physical Anthropology lab at the University of Granada (Spain) are considered to test our proposals.     

Command governor for constrained switched systems with scheduled model transition dwell times

In this paper, a switched control architecture for constrained control systems is presented. The strategy is based on command governor ideas that are here specialized to ‘optimally’ schedule switching events on the plant dynamics for improving control performance at the expense of low computational burdens. The significance of the method mainly lies in its capability to avoid constraints violation and loss of stability regardless of any configuration change occurrence in the plant/constraint structure. To this end, the concept of model transition dwell time is used within the proposed control framework to formally define the minimum time necessary to enable a switching event under guaranteed conditions on the overall stability and constraint fulfilment. Simulation results on a simple linear system and on a Cessna 182 aircraft model show the effectiveness of the proposed strategy. Copyright © 2017 John Wiley & Sons, Ltd.     

Male response to natural sex pheromone ofMigdolus fryanus westwood (Coleoptera: Cerambycidae) females as affected by daily climatic factors

Males of the sugarcane borer,Migdolus fryanus (Coleoptera: Cerambycidae), are attracted to females by means of a sex pheromone. Mating usually occurs during a few days from October to March under field conditions in São Paulo State, Brazil. This work reports on mating of this species as affected by daily climatic factors, during a single nuptial flight. Maximum male capture by the natural sex pheromone occurred from 1000 to 1100 AM at air and soil temperatures of 30.0°C and relative humidity of 57.0%. As these temperatures increased, females burrowed into the soil, as they are more sensitive to heat than males. Thus, it was concluded that sex pheromone-mediated mating in this cerambycid is directly affected by temperatures of air and soil.     

The phase behavior of n-alkane systems

Normal alkanes show very complicated phase transition kinetics and macroscopic phase equilibrium behavior. This paper focuses on the phase stability and equilibrium of complicated mixtures like n-alkanes and on the enabling global optimization technologies needed to gather problem knowledge. The new ideas contained in this paper include:

(1) novel level set methods for gathering encoded knowledge;

(2) the differential geometry for uncovering pathways to more subtle knowledge;

(3) all supporting non-linearly constrained optimization techniques;

(4) all data handling needed to unravel complex solution structure.

These new ideas are incorporated within the integral path methodology or terrain methods recently developed by Lucia, A., & Yang, F. (2003) [Lucia, A., & Yang F. (2003). Multivariable terrain methods. AIChE Journal 49, 2553] and Lucia, DiMaggio, and Depa (2004) [Lucia, A., DiMaggio, P.A., & Depa, P. (2004). A geometric terrain methodology for global optimization. Journal of Global Optimization 29, 297]. This framework provides global knowledge for understanding solution structure, like the complex solution structure of n-alkanes. In particular, it is shown that knowledge of the Newton and tangent vector fields, Gauss curvature, integral path bifurcation points, and non-differentiable manifolds provides a deterministic way of finding additional solutions, saddle points, and other information that might otherwise go undetected.It is shown that the optimization tools developed in this work provide all knowledge of interest on the appropriate hypothetical single-phase or composite surface (i.e., minima, saddle points, singular points, and integral paths) in phase stability applications. This knowledge can be obtained by solving the phase stability problem exactly once, in a pre-processing step, and used to reliably initialize any multi-phase equilibrium calculation for any feed. This removes the need to repeatedly solve the phase stability problem as the feed composition changes and greatly increases computational efficiency. Numerical examples and geometric illustrations are used to elucidate key ideas and to show how the proposed approach can be used to unravel the complicated phase behavior of n-alkane mixtures.