A look into fractional calculus and its applications from the signal processing point of view is done in this paper. A coherent approach to the fractional derivative is presented, leading to notions that are not only compatible with the classic but also constitute a true generalization. This means that the classic are recovered when the fractional domain is left. This happens in particular with the impulse response and transfer function. An interesting feature of the systems is the causality that the fractional derivative imposes. The main properties of the derivatives and their representations are presented. A brief and general study of the fractional linear systems is done, by showing how to compute the impulse, step and frequency responses, how to test the stability and how to insert the initial conditions. The practical realization problem is focussed and it is shown how to perform the input?ouput computations. Some biomedical applications are described.

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Today there is a strong interest in the scientific and industrial community concerning the use of biopolymers for electronic applications, mainly driven by low-cost and disposable applications. Adding to this interest, we must recognize the importance of the wireless auto sustained and low energy consumption electronics dream. This dream can be fulfilled by cellulose paper, the lightest and the cheapest known substrate material, as well as the Earth's major biopolymer and of tremendous global economic importance. The recent developments of oxide thin film transistors and in particular the production of paper transistors at room temperature had contributed, as a first step, for the development of disposable, low cost and flexible electronic devices. To fulfil the wireless demand, it is necessary to prove the concept of self powered devices. In the case of paper electronics, this implies demonstrating the idea of self regenerated thin film paper batteries and its integration with other electronic components. Here we demonstrate this possibility by actuating the gate of paper transistors by paper batteries. We found that when a sheet of cellulose paper is covered in both faces with thin layers of opposite electrochemical potential materials, a voltage appears between both electrodes -paper battery, which is also self-regenerated. The value of the potential depends upon the materials used for anode and cathode. An open circuit voltage of 0.5V and a short-circuit current density of 1$μ$A/cm2 were obtained in the simplest structure produced (Cu/paper/Al). For actuating the gate of the paper transistor, seven paper batteries were integrated in the same substrate in series, supplying a voltage of 3.4V. This allows proper ON/OFF control of the paper transistor. Apart from that transparent conductive oxides can be also used as cathode/anode materials allowing so the production of thin film batteries with transparent electrodes compatible with flexible, invisible, self powered and wireless electronics.

Tuberculosis (TB) is one of the leading causes of infection in humans, causing high morbility and mortality all over the world. The rate of new cases of multidrug resistant tuberculosis (MDRTB) continues to increase, and since these infections are very difficult to manage, they constitute a serious health problem. In most cases, drug resistance in Mycobacterium tuberculosis has been related to mutations in several loci within the pathogen's genome. The development of fast, cheap and simple screening methodologies would be of paramount relevance for the early detection of these mutations, essential for the timely and effective diagnosis and management of MDRTB patients. The use of gold nanoparticles derivatized with thiol-modified oligonucleotides (Au-nanoprobes) has led to new approaches in molecular diagnostics. Based on the differential non-cross-linking aggregation of Au-nanoprobes, we were able to develop a colorimetric method for the detection of specific sequences and to apply this approach to pathogen identification and single base mutations/single nucleotide polymorphisms (SNP) discrimination. Here we report on the development of Au-nanoprobes for the specific identification of SNPs within the beta subunit of the RNA polymerase (rpoB locus), responsible for resistance to rifampicin in over 95% of rifampicin resistant M. tuberculosis strains.

The investigation of 3,4-methylenedioxymethamphetamine (MDMA: ecstasy) abuse requires very robust methods with high sensitivity and wide linearity ranges for the quantification of this drug of abuse and its main metabolites in body fluids. An optimized gas chromatography-ion trap mass spectrometry (GC-IT/MS) methodology with electron impact ionization addressing these issues is presented. The sample preparation involves an enzymatic hydrolysis of urine and plasma for conjugate cleavage, a SPE extraction, and a derivatization process. The method was fully validated in rat plasma and urine. Linearity for a wide concentration range was achieved for MDMA, and the metabolites 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine (HMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA). Limits of quantification were 2 ng/mL in plasma and 3.5 ng/mL in urine using a Selected Ion Monitoring detection mode. Selectivity, accuracy, precision, and recovery met the required criteria for the method validation. This GC-IT/MS method provides high sensitivity and adequate performance characteristics for the simultaneous quantification of MDMA, MDA, HMA and HMMA in the studied matrices. (C) 2010 Elsevier B.V. All rights reserved.

Pseudoazurins are small type 1 copper proteins that are involved in the flow of electrons between various electron donors and acceptors in the bacterial periplasm, mostly under denitrifying conditions. The previously determined structure of Paracoccus pantotrophus pseudoazurin in the oxidized form was improved to a nominal resolution of 1.4 angstrom, with R and R(free) values of 0.188 and 0.206, respectively. This high-resolution structure makes it possible to analyze the interactions between the monomers and the solvent structure in detail. Analysis of the high-resolution structure revealed the structural regions that are responsible for monomer-monomer recognition during dimer formation and for protein-protein interaction and that are important for partner recognition. The pseudoazurin structure was compared with other structures of various type 1 copper proteins and these were grouped into families according to similarities in their secondary structure; this may be useful in the annotation of copper proteins in newly sequenced genomes and in the identification of novel copper proteins.

We recently reported on the use of caged nucleotides to attain full control of enzymatic polymerization of RNA solely by light. In the absence of light no RNA formation was possible due to the efficient caging by the coumarin moiety; after irradiation, caged ATP was released with quantitative precision and RNA polymerization was resumed. As photolabile protecting group [7-(diethylamino) coumarin-4-yl]methyl] (DEACM) was used due to its high absorbance in the visible region of the spectrum, fast deprotection kinetics and absence of radical intermediates. However, the 7-diethylamino-4-hydroxymethylcoumarin photo-product (DEACM-OH) was shown to inhibit the transcription reaction for concentrations higher than 30 μM [5]. This inhibition has been associated with poor water solubility, which is commonly dealt with via cumbersome chemical modifications of the protecting moiety. To overcome inhibition, we evaluated the use of molecular scavengers to sequester DEACM-OH formed after irradiation. Determination of association constants of coumarin with β-cyclodextrins allowed the assessment of its capability to remove free coumarin molecules from solution. The influence of β-cyclodextrin in transcription reaction was also assessed. Results show that β-cyclodextrin can be successfully used as scavenger as it increases the DEACM-OH threshold concentration for inhibition, amplifying the efficiency of light controlled in vitro transcription.

The derivatization of gold-silver alloy nanoparticles with thiol-ssDNA oligonucleotides (AuAg-alloy-nanoprobes) and their use in nucleic acid detection is presented. A non-cross-linking method has been previously developed by our group using gold nanoparticles, which is based on the colorimetric comparison of solutions before and after salt-induced nanoprobe aggregation. Only the presence of a complementary target stabilizes the nanoprobe, preventing aggregation and colorimetric change after salt addition. Through this approach, the AuAg-alloy-nanoprobes allowed to specifically detect a sequence derived from the RNA polymerase β-subunit gene of Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, with a 2.5-fold enhanced sensitivity (0.3 μg of total DNA) when compared to their gold counterparts.

The effect of kefir grains on the proteolysis of major milk proteins in milk kefir and in a culture of kefir grains in pasteurized cheese whey was followed by reverse phase-HPLC analysis. The reduction of kappa-, alpha-, and beta-caseins (CN), alpha-lactalbumin (alpha-LA), and beta-lactoglobulin (beta-LG) contents during 48 and 90 h of incubation of pasteurized milk (100 mL) and respective cheese whey with kefir grains (6 and 12 g) at 20 degrees C was monitored. Significant proteolysis of alpha-LA and kappa-, alpha-, and beta-caseins was observed. The effect of kefir amount (6 and 12 g/100 mL) was significant for alpha-LA and alpha- and beta-CN. alpha-Lactalbumin and beta-CN were more easily hydrolyzed than alpha-CN. No significant reduction was observed with respect to beta-LG concentration for 6 and 12 g of kefir in 100 mL of milk over 48 h, indicating that no significant proteolysis was carried out. Similar results were observed when the experiment was conducted over 90 h. Regarding the cheese whey kefir samples, similar behavior was observed for the proteolysis of alpha-LA and beta-LG: alpha-LA was hydrolyzed between 60 and 90% after 12 h (for 6 and 12 g of kefir) and no significant beta-LG proteolysis occurred. The proteolytic activity of lactic acid bacteria and yeasts in kefir community was evaluated. Kefir milk prepared under normal conditions contained peptides from proteolysis of alpha-LA and kappa-, alpha-, and beta-caseins. Hydrolysis is dependent on the kefir: milk ratio and incubation time. beta-Lactoglobulin is not hydrolyzed even when higher hydrolysis time is used. Kefir grains are not appropriate as adjunct cultures to increase beta-LG digestibility in whey-based or whey-containing foods.

There are numerous reports of coumarin ester derivatives, in particular phosphate esters, as photocleavable cages in biological systems. Despite the comprehensive analysis of the photocleavage mechanism, studies of 4-methylcoumarin caged phosphates and/or nucleotides were always performed at constant pH. In this work, we present the study of the pH effect on the photochemistry of (7-diethylaminocoumarin-4-yl)methyl phosphate (DEACM-P). Fluorescence and photocleavage quantum yields, as well as the fluorescence decay times were measured as a function of the pH. It was found that the pH produces significant changes in the overall photochemical quantum yield of DEACM-P, and the observed changes are complementary to those obtained from the fluorescence quantum yield. Deprotonation of DEACM-HPO4 - to yield DEACM-PO4 2-, produces a decrease in the photochemical quantum yield (from 0.0045 to 0.0003) and an increase in the fluorescence quantum yield (from 0.072 to 0.092). Moreover, from the analysis of the decay times, we have also found that hydroxyl ion is not only relevant, but it is mechanistically involved in the photoreaction of DEACM-HPO4 -.