Synthesis, Structure and Antitumour Properties of a New 1,2-Propylenediaminetetraacetate-Ruthenium(III) Compound

A novel complex formed by ruthenium (III) and the sequestering ligand 1,2-propylenediaminetetraacetic acid (PDTA) has been synthetized and characterized. The structure of the monomeric compound, studied by X-ray diffraction , shows an almost symmetric octahedral geometry around the metal ion, with two chlorine atoms in a cis conformation. The antitumour activity against a variety of murine and human cancers is reported.     

Deformability properties of timolol-loaded transfersomes based on the extrusion mechanism. Statistical optimization of the process

The purpose of this work was to analyze the deformability properties of different timolol maleate (TM)-loaded transfersomes by extrusion. This was performed because elastic liposomes may contribute to the elevation of amount and rate of drug permeation through the corneal membrane. This paper describes the optimization of a transfersome formulation by use of Taguchi orthogonal experimental design and two different statistical analysis approaches were utilized. The amount of cholesterol (F1), the amount of edge-activator (F2), the distribution of the drug into the vesicle (F3), the addition of stearylamine (F4) and the type of edge-activator (F5) were selected as causal factors. The deformability index, the phosphorous recovery, the vesicle size, the polydispersity index, the zeta potential and percentage of drug entrapped were fixed as the dependent variables and these responses were evaluated for each formulation. Two different statistical analysis approaches were applied. The better statistical approach was determined by comparing their prediction errors, where regression analysis provided better optimized responses than marginal means. From the study, an optimized formulation of TM-loaded transfersomes was prepared and obtained for the proposed ophthalmic delivery for the treatment of open angle glaucoma. It was found that the lipid to surfactant ratio and type of surfactant are the main key factors for determining the flexibility of the bilayer of transfersomes. From in vitro permeation studies, we can conclude that TM-loaded transfersomes may enhance the corneal transmittance and improve the bioavailability of conventional TM delivery.     

GraftFast Surface Engineering to Improve MOF Nanoparticles Furtiveness

Controlling the outer surface of nanometric metal–organic frameworks (nanoMOFs) and further understanding the in vivo effect of the coated material are crucial for the convenient biomedical applications of MOFs. However, in most studies, the surface modification protocol is often associated with significant toxicity and/or lack of selectivity. As an alternative, how the highly selective and general grafting GraftFast method leads, through a green and simple process, to the successful attachment of multifunctional biopolymers (polyethylene glycol (PEG) and hyaluronic acid) on the external surface of nanoMOFs is reported. In particular, effectively PEGylated iron trimesate MIL‐100(Fe) nanoparticles (NPs) exhibit suitable grafting stability and superior chemical and colloidal stability in different biofluids, while conserving full porosity and allowing the adsorption of bioactive molecules (cosmetic and antitumor agents). Furthermore, the nature of the MOF–PEG interaction is deeply investigated using high‐resolution soft X‐ray spectroscopy. Finally, a cell penetration study using the radio‐labeled antitumor agent gemcitabine monophosphate (³H‐GMP)‐loaded MIL‐100(Fe)@PEG NPs shows reduced macrophage phagocytosis, confirming a significant in vitro PEG furtiveness.     

Detection of IgM against the dengue++ virus in whole blood absorbed on filter paper]

Thirty-four sheep were submitted to surgery substituting the native ACL with the central third of the patellar tendon, ten enter this study. The purpose was to find a possible relationship between tissue pO2 and healing processes considering also the biomechanical and histomorphological aspects of the grafts. Four of them were sacrificed under general anaesthesia after 6 months, and six after 1 year in order to perform tissue pO2 measurement and an analysis of microvessel density on specimens of the normal ACL and the graft. Our data showed higher pO2 values of the autografts after 6 months. After 1 year the data was comparable to those of native ACL. This was confirmed by a microvessel count of the histological specimens and the data was in relationship to biomechanical and histomorphological analysis. Tissue pO2 can be observed and recorded in "in vivo" ACL, and patellar tendon used as graft, with no injury to their integrity. The monitoring system might be considered as an experimental tool for indirect controls of the anterior cruciate substitutes.     

The resting and activation issue of hypofrontality: a single photon emission computed tomography study in neuroleptic-naive and neuroleptic-free schizophrenic female patients

BACKGROUND: Functional neuroimaging findings of "hypofrontality" in schizophrenic patients is still controversial, due to the heterogeneity of methods and patient samples. This study tries to prevent some of these concerns by studying neuroleptic-naive (NN) and neuroleptic-free (NF) young female patients both in resting conditions and during a frontal cognitive activation task. METHODS: Regional cerebral blood flow (rCBF) was studied at rest and during the Wisconsin Card Sorting Test (WCST) in 25 young acute unmedicated schizophrenic female patients (14 NN and 11 NF) and 15 female controls, using single photon emission computed tomography. RESULTS: The schizophrenic and control groups did not differ in rCBF during the baseline condition, but the schizophrenic group failed to activate the frontal lobe during the WCST condition. In addition, the left anterior temporal rCBF at rest correlated with the Scale for the Assessment of Positive Symptoms total score. CONCLUSIONS: The results suggest that hypofrontality in young acute unmedicated schizophrenic patients is a result of an inability to activate frontal regions during cognition, rather than a baseline decrease in frontal activity. Furthermore, positive symptoms seem to be associated with left temporal cortex activity.     

Partitioned formulation of internal and gravity waves interacting with flexible structures

This paper presents a partitioned modeling of internal and gravity fluid waves that interact with flexible structures. The governing interaction model consists of three completely partitioned entities: fluid model, structural model, and interface model that acts as an internal constraint on the fluid–structure interface boundary. Thus, the proposed partitioned multi-physics modeling can employ two completely modular fluid and structure software modules plus an interface solver, hence amenable to partitioned solution algorithms. The interface discretization can exploit the nonmatching interface algorithm previously developed via the method of localized Lagrange multipliers. Also noted is that the present fluid model can make use of widely available finite element software for standard Poisson-type problems.     

Optimization of biochemical systems through mathematical programming: Methods and applications

In this work we present a general (mono and multiobjective) optimization framework for the technological improvement of biochemical systems. The starting point of the method is a mathematical model in ordinary differential equations (ODEs) of the investigated system, based on qualitative biological knowledge and quantitative experimental data. In the method we take advantage of the special structural features of a family of ODEs called power-law models to reduce the computational complexity of the optimization program. In this way, the genetic manipulation of a biochemical system to meet a certain biotechnological goal can be expressed as an optimization program with some desired properties such as linearity or convexity.The general method of optimization is presented and discussed in its linear and geometric programming versions. We furthermore illustrate the use of the method by several real case studies. We conclude that the technological improvement of microorganisms can be afforded using the combination of mathematical modelling and optimization. The systematic nature of this approach facilitates the redesign of biochemical systems and makes this a predictive exercise rather than a trial-and-error procedure.     

A formal analysis of database replication protocols with SI replicas and crash failures

This paper provides a formal specification and proof of correctness of a basic Generalized Snapshot Isolation certification-based data replication protocol for database middleware architectures. It has been modeled using a state transition system, as well as the main system components, allowing a perfect match with the usual deployment in a middleware system. The proof encompasses both safety and liveness properties, as it is commonly done for a distributed algorithm. Furthermore, a crash failure model has been assumed for the correctness proof, although recovery analysis is not the aim of this paper. This allows an easy extension toward a crash-recovery model support in future works. The liveness proof focuses in the uniform commit: if a site has committed a transaction, the rest of sites will either commit it or it would have crashed.     

A multivariable control scheme in a two-stage anaerobic digestion system described by partial differential equations

This paper deals with the design and application of a nonlinear multivariable controller in an anaerobic digestion system (AD) carried out in two interconnected fixed bed bioreactors. The proposed control scheme is derived from a mathematical model of the AD system described by a set of partial differential equations and consists of an estimator and two nonlinear control laws. The first law is developed to regulate the volatile fatty acids in the first bioreactor while the second aims at maintaining the chemical oxygen demand at predetermined set-points in the second bioreactor. The performance of the control algorithm is evaluated via numerical simulations in the face of load disturbances, parameter kinetic uncertainties and set-point changes. Stability and convergence properties of the proposed control scheme are also addressed in this paper.