Effective treatment of infectious diseases: A nonlinear adaptive control theoretic approach

A nonlinear adaptive system theoretic approach is presented in this paper for effective treatment of infectious diseases that affect various organs of the human body. The generic model used does not represent any specific disease. However, it mimics the generic immunological dynamics of the human body under pathological attack, including the response to external drugs. From a system theoretic point of view, drugs can be interpreted as control inputs. Assuming a set of nominal parameters in the mathematical model, first a nonlinear controller is designed based on the principle of dynamic inversion. This treatment strategy was found to be effective in completely curing "nominal patients". However, in some cases it is ineffective in curing "realistic patients". This leads to serious (sometimes fatal) damage to the affected organ. To make the drug dosage design more effective, a model-following neuro-adaptive control design is carried out using neural networks, which are trained (adapted) online. From simulation studies, this adaptive controller is found to be effective in killing the invading microbes and healing the damaged organ even in the presence of parameter uncertainties and continuing pathogen attack.

A neuro-adaptive augmented optimal dynamic inversion approach for effective and efficient treatment of chronic myelogenous leukemia

Combining the advanced techniques of optimal dynamic inversion and model-following neuro-adaptive control design, an efficient technique is presented for effective treatment of chronic myelogenous leukemia (CML). A recently developed nonlinear mathematical model for cell dynamics is used for the control (medication) synthesis. First, taking a set of nominal parameters, a nominal controller is designed based on the principle of optimal dynamic inversion. This controller can treat nominal patients (patients having same nominal parameters as used for the control design) effectively. However, since the parameters of an actual patient can be different from that of the ideal patient, to make the treatment strategy more effective and efficient, a model-following neuro-adaptive controller is augmented to the nominal controller. In this approach, a neural network trained online (based on Lyapunov stability theory) facilitates a new adaptive controller, computed online. From the simulation studies, this adaptive control design approach (treatment strategy) is found to be very effective to treat the CML disease for actual patients. Sufficient generality is retained in the theoretical developments in this paper, so that the techniques presented can be applied to other similar problem as well. Note that the technique presented is computationally non-intensive and all computations can be carried out online.

Probing Fluorine Interactions in a Polyhydroxylated Environment: Conservation of a C-F center dot center dot center dot H-C Recognition Motif in Presence of O-H center dot center dot center dot O Hydrogen Bonds

Three conformationally locked fluorinated polycyclitols have been specially crafted on a rigid trans-decalin backbone, employing a surprisingly facile pyridine-poly(hydrogen fluoride)-mediated stereospecific epoxide ring opening as the key reaction. Molecula design of the three fluorinated probes under study focused on providing an efficient platform for (a) evaluating the ability of covalently bonded fluorine, vis-a-vis the isosteric hydroxy group, to act as a H-bond acceptor and (b) examining the possibility for an organic fluorine moiety, placed suitably in a spatially invariant position, to engage an 1,3-diaxial OH functionality in a purported intramolecular O-H center dot center dot center dot F hydrogen bond. The present endeavour reveals that C(sp(3))-F center dot center dot center dot H-C(sp(3)) hydrogen bonds, though weak and lesser investigated, can indeed be observed and supramolecular recognition motifs, involving such interactions, can be conserved even in crystal structures laden with stronger O-H center dot center dot center dot O hydrogen bonds.

Molecular and crystal structure of 4-ethynylcyanobenzene. An example of Csingle bondHcdots, three dots, centeredN hydrogen bonding

The molecular and crystal structures of 4-ethynylcyanobenzene arereported. The packing of molecules in the crystal is found to be homologous with the crystal structures of HCN, cyanoacetylene and 4-cyano-4'-ethynylbiphenyl. Alternatively, these four crystals could be said to constitute a structural homologous series. The influence of C-H center dot center dot center dot N hydrogen bonding in directing a linear supramolecular arrangement of molecules with ethynyl and cyano groups at opposite ends, is illustrated. (C) 2010 Elsevier B.V. All rights reserved.

Electronic-Transitions In Hydrogen-Bonded Dimers Of Carboxylic-Acids In The Vapor-Phase - An Electron-Energy Loss Spectroscopic Study

An electron energy loss spectroscopic study of the formic acid dimer has shown bands centred around 7.2, 8.5, 9.8, and 11.1 eV, of which the first and the third bands are assigned to n- rc* transitions and the other two to n-n* transitions; similar transitions are found in the acetic acid dimer.

Plasticity in the primary binding site of galactose/N-acetylgalactosamine-specific lectins - Implication of the C-H center dot center dot center dot O hydrogen bond at the specificity-determining C-4 locus of the saccharide in 4-methoxygalactose recognition by jacalin and winged bean (basic) agglutinin I

It is currently believed that an unsubstituted axial hydroxyl at the specificity-determining C-4 locus of galactose is indispensable for recognition by galactose/N-acetylgalactosamine-specific lectins. Titration calorimetry demonstrates that 4-methoxygalactose retains binding allegiance to the Moraceae lectin jacalin and the Leguminosae lectin, winged bean (basic) agglutinin (WBA I). The binding reactions were driven by dominant favorable enthalpic contributions and exhibited significant enthalpy-entropy compensation. Proton NMR titration of C-methoxygalactose with jacalin and WBA I resulted in broadening of the sugar resonances without any change in chemical shift. The alpha-and beta-anomers of 4-methoxygalactose were found to be in slow exchange with free and lectin-bound states. Both the anomers experience magnetically equivalent environments at the respective binding sites. The binding constants derived from the dependence of NMR line widths on 4-methoxygalactose concentration agreed well with those obtained from titration calorimetry. The results unequivocally demonstrate that the loci corresponding to the axially oriented C-4 hydroxyl group of galactose within the primary binding site of these lectins exhibit plasticity. These analyses suggest, for the first time, the existence of C-H ... O-type hydrogen-bond(s) in protein-carbohydrate interactions in general and between the C-4 locus of galactose derivative and the lectins jacalin and WBA I in particular.

An unusual C-H center dot center dot center dot O hydrogen bond mediated reversal of polypeptide chain direction in a synthetic peptide helix

An unusual C-terminal conformation has been detected in a synthetic decapeptide designed to analyze the stereochemistry of helix termination in polypeptides. The crystal structure of the decapeptide Boc-Leu-Aib-Val-Ala-Leu-Aib-Val-(D)Ala-(D)Leu-Aib-OMe reveals a helical segment spanning residues 1-7 and helix termination by formation of a Schellman motif, generated by (D)Ala(8) adopting the left-handed helical (alpha(L)) conformation. The extended conformation at (D)Leu(9) results in a compact folded structure, stabilized by a potentially strong C-H ... O hydrogen bond between Ala(4) (CH)-H-alpha and (D)Leu(9)CO. The parameters for C-H ... O interaction are Ala(4) (CH)-H-alpha .. O=C (D)Leu(9) distance 3.27 Angstrom C-alpha-H .. O angle 176 degrees, and O .. H-alpha distance 2.29 Angstrom. This structure suggests that insertion of contiguous D-residues may provide a handle for the generation of designed structures containing more than one helical segment folded in a compact manner. (C) 2000 Academic Press.

Electrochemical investigation of single-walled carbon nanotubes for hydrogen storage

Electrodes made of purified and open single walled carbon nanotubes behave like metal hydride electrodes in Ni-MH batteries, showing high electrochemical reversible charging capacity up to 800 mAh g(-1) corresponding to a hydrogen storage capacity of 2.9 wt% compared to known AB(5), AB(2) metal hydride electrodes. (C) 2000 Elsevier Science Ltd. All rights reserved.

Ab-initio molecular orbital studies on C---H…X hydrogen bonded systemsstar

C---H…X hydrogen bonded systems are studied by the STO-3G method. The proton donor ability of carbon is analysed in terms of its hybridization states and the substituents.

Nature of hydrogen atom trapped inside palladium lattice

Colloid of palladium nanoparticles has been prepared by the Solvated Metal Atom Dispersion (SMAD) method. Reaction of Pd(0) nanopowder obtained upon precipitation from the colloid, with ammonia borane (H3N center dot BH3, AB) in aqueous solutions at room temperature results in the generation of active hydrogen atoms. The active hydrogen atoms either combine with one another resulting in H-2 evolution or diffuse into the Pd lattice to afford PdHx. Diffusion of hydrogen atoms leads to an expansion of the Pd lattice. The diffused hydrogen atoms are distributed uniformly over the entire particle. These features were established using powder XRD and electron microscopy studies. The H-1 NMR spectral studies of PdHx before and after desorption of H-2 revealed that the hydrogen atoms trapped inside Pd lattice are hydridic in nature. Desorption of hydrogen from PdHx did not result in complete reversibility suggesting that some hydrogen atoms are strongly trapped inside the Pd lattice. (C) 2010 Professor T. Nejat Veziroglu. Published by Elsevier Ltd. All rights reserved.

Influence of substrate temperature and post-deposition heat treatment on the optical properties of SiO2 films

Silicon dioxide films are extensively used as protective, barrier and also low index films in multilayer optical devices. In this paper, the optical properties of electron beam evaporated SiO2 films, including absorption in the UV, visible and IR regions, are reported as a function of substrate temperature and post-deposition heat treatment. A comparative study of the optical properties of SiO2 films deposited in neutral and ionized oxygen is also made.

Formation and crystallization of hydrogen-induced amorphous SmFe2H3.6 alloy

On hydrogenation of the Laves phase SmFe2, an amorphous SmFe2H3.6 (a-SmFe2H3.6) alloy was formed between 400 K and 500 K. The amorphous nature of the alloy was confirmed by X-ray diffraction, transmission electron microscopy and thermal analysis. However, SmFe2 absorbed hydrogen in the crystal state below 350 K and decomposed into SmH2 and α-Fe above 550 K. The crystallization behaviour of a-SmFe2H3.6 was investigated by differential scanning calorimetry in combination with electron microscopy. Even after considerable hydrogen desorption (Image ) by an endothermic reaction on heating, the amorphous state was retained. Crystallization of a-SmFe2H3.6 took place in two stages. The first stage involved the precipitation of α-Fe in the amorphous matrix. The second stage involved the decomposition of the remaining amorphous phase into the equilibrium phases SmH2 and SmFe2.

Conformations of three heterocyclicperhydropyrrolobenzofurans and polymeric assembly via co-operative inter-molecular C-H center dot center dot center dot O hydrogen bonds

In 1-cyclo-hexyl-6,6,8a-trimethyl-3a,6,7,8a-tetra-hydro-1H-1-benzofuro[2,3-b]pyrrole-2,4(3H,5H)-dione, C19H27NO3, (I), and the isomorphous compounds 6,6,8a-trimethyl-1-phenyl-3a,6,7,8a-tetra-hydro-1H-1-benzofuro[2,3-b]pyrrole-2,4(3H,5H)-dione, C19H21NO3, (II), and 6,6,8a-trimethyl-1-(3-pyridyl)-3a,6,7,8a-tetra-hydro-1H-1-benzofuro[2,3-b]pyrrole-2,4(3H,5H)-dione, C18H20N2O3, (III), the tetra-hydro-benzo-dihydro-furo-pyrrolidine ring systems are folded at the cis junction of the five-membered rings, giving rise to a non-planar shape of the tricyclic cores. The dihydro-furan and pyrrolidine rings in (I) are puckered and adopt an envelope conformation. The cyclo-hexene rings adopt a half-chair conformation in all the mol-ecules, while the substituent N-cyclo-hexyl ring in (I) assumes a chair form. Short intra-molecular C-HcO contacts form S(5) and S(6) motifs. The isomorphous compounds (II) and (III) are effectively isostructural, and aggregate into chains via inter-molecular C-HcO hydrogen bonds.

Simplified Treatment of Childhood Acute Bone and Joint Infections

Acute childhood osteomyelitis (OM), septic arthritis (SA), and their combination osteomyelitis with adjacent septic arthritis (OM+SA), are treated with long courses of antimicrobials and immediate surgery. We conducted a prospective multi-center randomized trial among Finnish children at age 3 months to 15 years in 1983-2005. According to the two-by-two factorial study design, children with OM or OM+SA received 20 or 30 days of antimicrobials, whereas those with SA were treated for 10 or 30 days. In addition, the whole series was randomized to be treated with clindamycin or a first-generation cephalosporin. Cases were included only if the causative agent was isolated. The treatment was instituted intravenously, but only for the first 2-4 days. Percutaneous aspiration was done to obtain a representative sample for bacteriology, but all other surgical intervention was kept at a minimum. A total of 265 patients fulfilled our strict inclusion criteria and were analyzed; 106 children had OM, 134 SA, and 25 OM+SA. In the OM group, one child in the long and one child in the short-term treatment group developed sequelae. One child with SA twice developed a late re-infection of the same joint, but the causative agents differed. Regarding surgery, diagnostic arthrocentesis or corticotomy was the only surgical procedure performed in most cases. Routine arthrotomy was not required even in hip arthritis. Serum C-reactive protein (CRP) proved to be a reliable laboratory index in the diagnosis and monitoring of osteoarticular infections. The recovery rate was similar regardless of whether clindamycin or a first-generation cephalosporin was used. We conclude that a course of 20 days of these well-absorbing antimicrobials is sufficient for OM or OM+SA, and 10 days for SA in most cases beyond the neonatal age. A short intravenous phase of only 2-5 days often suffices. CRP gives valuable information in monitoring the course of illness. Besides diagnostic aspiration, surgery should be reserved for selected cases.