Analytical solutions for diffuse fluorescence spectroscopy/imaging in biological tissues. Part I: zero and extrapolated boundary conditions

The mathematical model for diffuse fluorescence spectroscopy/imaging is represented by coupled partial differential equations (PDEs), which describe the excitation and emission light propagation in soft biological tissues. The generic closed-form solutions for these coupled PDEs are derived in this work for the case of regular geometries using the Green's function approach using both zero and extrapolated boundary conditions. The specific solutions along with the typical data types, such as integrated intensity and the mean time of flight, for various regular geometries were also derived for both time-and frequency-domain cases. (C) 2013 Optical Society of America

Effects of different modes of hot cross-rolling in 7010 aluminum alloy: part I. evolution of microstructure and texture

The current study describes the evolution of microstructure and texture in an Al-Zn-Mg-Cu-Zr-based 7010 aluminum alloy during different modes of hot cross-rolling. Processing of materials involves three different types of cross-rolling. The development of texture in the one-step cross-rolled specimen can be described by a typical beta-fiber having the maximum intensity near Copper (Cu) component. However, for the multi-step cross-rolled specimens, the as-rolled texture is mainly characterized by a strong rotated-Brass (Bs) component and a very weak rotated-cube component. Subsequent heat treatment leads to sharpening of the major texture component (i.e., rotated-Bs). Furthermore, the main texture components in all the specimens appear to be significantly rotated in a complex manner away from their ideal positions because of non-symmetric deformations in the two rolling directions. Detailed microstructural study indicates that dynamic recovery is the dominant restoration mechanism operating during the hot rolling. During subsequent heat treatment, static recovery dominates, while a combination of particle-stimulated nucleation (PSN) and strain-induced grain boundary migration (SIBM) causes partial recrystallization of the grain structure. The aforementioned restoration mechanisms play an important role in the development of texture components. The textural development in the current study could be attributed to the combined effects of (a) cross-rolling and inter-pass annealing that reduce the intensity of Cu component after each successive pass, (b) recrystallization resistance of Bs-oriented grains, (c) stability of Bs texture under cross-rolling, and (d) Zener pinning by Al3Zr dispersoids.

Microstructure and texture evolution during sub-transus thermomechanical processing of Ti-6Al-4V-0.1B alloy: part I. hot rolling in (alpha plus beta) phase field

In the current study, the evolution of microstructure and texture has been studied for Ti-6Al-4V-0.1B alloy during sub-transus thermomechanical processing. This part of the work deals with the deformation response of the alloy by rolling in the (alpha + beta) phase field. The (alpha + beta) annealing behavior of the rolled specimen is communicated in part II. Rolled microstructures of the alloys exhibit either kinked or straight alpha colonies depending on their orientations with respect to the principal rolling directions. The Ti-6Al-4V-0.1B alloy shows an improved rolling response compared with the alloy Ti-6Al-4V because of smaller alpha lamellae size, coherency of alpha/beta interfaces, and multiple slip due to orientation factors. Accelerated dynamic globularization for this alloy is similarly caused by the intralamellar transverse boundary formation via multiple slip and strain accumulation at TiB particles. The (0002)(alpha) pole figures of rolled Ti-6Al-4V alloy shows ``TD splitting'' at lower rolling temperatures because of strong initial texture. Substantial beta phase mitigates the effect of starting texture at higher temperature so that ``RD splitting'' characterizes the basal pole figure. Weak starting texture and easy slip transfer for Ti-6Al-4V-0.1B alloy produce simultaneous TD and RD splittings in basal pole figures at all rolling temperatures.

On the Chern number of I-admissible filtrations of ideals

Let I be an m-primary ideal of a Noetherian local ring (R, m) of positive dimension. The coefficient e(1)(I) of the Hilbert polynomial of an I-admissible filtration I is called the Chern number of I. A formula for the Chern number has been derived involving the Euler characteristic of subcomplexes of a Koszul complex. Specific formulas for the Chern number have been given in local rings of dimension at most two. These have been used to provide new and unified proofs of several results about e(1)(I).

Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation I as augmentation therapeutic strategy approaches in muscular dystrophy

Backgrond: Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. Methods: In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. Results: The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

Synthon modularity in Cocrystals of 4-Bromobenzamide with n-Alkanedicarboxylic acids: type I and type ll Halogen center dot center dot center dot Halogen interactions

A Cambridge Structural Database (CSD) analysis on halogen center dot center dot center dot halogen contacts (X...X) in organic crystals has been carried out to review the classification criteria for type I, type II, and quasi type I/II halogen interactions. Trends observed in previous CSD analyses of the phenomenon are reinforced in the present study. The manner in which these interactions are manifested in cocrystals of 4-bromobenzamide and dicarboxylic acid is examined. The design strategy for these cocrystals uses synthon theory and follows from an understanding of the crystal structures of gamma-hydroquinone and a previously studied set of 4-hydroxybenzamide dicarboxylic acid cocrystals, making use of Br/OH isostructurality. All cocrystals are obtained by clean insertion of dicarboxylic acids between 4-bromobenzamide molecules. The strategy is deliberate and the prediction of synthons done well in advance, as evidenced from the robustness of the acid-amide heterosynthons in all nine crystal structures, with no aberrant structures in the crystallization experiments. Formation of the acid-amide synthon in these cocrystals is identified with IR spectroscopy. The packing in these cocrystals can be distinguished in terms of whether the Br...Br interactions are type I or II. Eight sets of dimorphs were retrieved from the CSD, wherein the basis of the polymorphism is that one crystal has a type I Br...Br interaction, while the other has a type II interaction.

Carboxyl terminal domain basic amino acids of mycobacterial topoisomerase I bind DNA to promote strand passage

Bacterial DNA topoisomerase I (topoI) carries out relaxation of negatively supercoiled DNA through a series of orchestrated steps, DNA binding, cleavage, strand passage and religation. The N-terminal domain (NTD) of the type IA topoisomerases harbor DNA cleavage and religation activities, but the carboxyl terminal domain (CTD) is highly diverse. Most of these enzymes contain a varied number of Zn2+ finger motifs in the CTD. The Zn2+ finger motifs were found to be essential in Escherichia coli topoI but dispensable in the Thermotoga maritima enzyme. Although, the CTD of mycobacterial topoI lacks Zn2+ fingers, it is indispensable for the DNA relaxation activity of the enzyme. The divergent CTD harbors three stretches of basic amino acids needed for the strand passage step of the reaction as demonstrated by a new assay. We also show that the basic amino acids constitute an independent DNA-binding site apart from the NTD and assist the simultaneous binding of two molecules of DNA to the enzyme, as required during the catalytic step. Although the NTD binds to DNA in a site-specific fashion to carry out DNA cleavage and religation, the basic residues in CTD bind to non-scissile DNA in a sequence-independent manner to promote the crucial strand passage step during DNA relaxation. The loss of Zn2+ fingers from the mycobacterial topoI could be associated with Zn2+ export and homeostasis.

Generation of Ligand Specificity and Modes of Oligomerization in beta-Prism I Fold Lectins

beta-Prism I fold lectins constitute one of the five widely occurring structural classes of plant lectins. Each single domain subunit is made up of three Greek key motifs arranged in a threefold symmetric fashion. The threefold symmetry is not reflected in the sequence except in the case of the lectin from banana, a monocot, which carries two sugar-binding sites instead of the one in other lectins of known three-dimensional structure, all from dicots. This is believed to be a consequence of the different evolutionary paths followed by the lectin in monocots and dicots. The galactose-specific lectins among them have two chains produced by posttranslational proteolysis and contain three aromatic residues at the binding site. The extended binding sites of galactose- and mannose-specific lectins have been thoroughly characterized. Ligand binding at the sites involves both conformational selection and induced fit. Molecular plasticity of some of the lectins in the family has been characterized. The plasticity appears to be such as to promote variability in quaternary association which could be dimeric, tetrameric, or octameric. Structural and evolutionary reasons for the variability have been explored, and the relation of oligomerization to ligand binding and conformational selection investigated.

Conditional silencing of topoisomerase I gene of Mycobacterium tuberculosis validates its essentiality for cell survival

Topoisomerases are an important class of enzymes for regulating the DNA transaction processes. Mycobacterium tuberculosis (Mtb) is one of the most formidable pathogens also posing serious challenges for therapeutic interventions. The organism contains only one type IA topoisomerase (Rv3646c), offering an opportunity to test its potential as a candidate drug target. To validate the essentiality of M.tuberculosis topoisomerase I (TopoI(Mt)) for bacterial growth and survival, we have generated a conditionally regulated strain of topoI in Mtb. The conditional knockdown mutant exhibited delayed growth on agar plate. In liquid culture, the growth was drastically impaired when TopoI expression was suppressed. Additionally, novobiocin and isoniazid showed enhanced inhibitory potential against the conditional mutant. Analysis of the nucleoid revealed its altered architecture upon TopoI depletion. These studies establish the essentiality of TopoI for the M.tuberculosis growth and open up new avenues for targeting the enzyme.

Effects of temperature on complexes I and II mediated respiration, ROS generation and oxidative stress status in isolated gill mitochondria of the mud crab Scylla serrata

Effects of fluctuations in habitat temperature (18-30 degrees) on mitochondrial respiratory behavior and oxidative metabolic responses in the euryhaline ectotherm Scylla serrate are not fully understood. In the present study, effects of different temperatures ranging from 12 to 40 degrees C on glutamate and succinate mediated mitochondrial respiration, respiratory control ratio (RCR), ATP generation rate, ratio for the utilization of phosphate molecules per atomic oxygen consumption (P/O), levels of lipid peroxidation and H2O2 in isolated gill mitochondria of S. serrata are reported. The pattern of variation in the studied parameters was similar for the two substrates at different temperatures. The values recorded for RCR ( >= 3) and P/O ratio (1.4-2.7) at the temperature range of 15-25 degrees C were within the normal range reported for other animals (3-10 for RCR and 1.5-3 for P/O). Values for P/O ratio, ATP generation rate and RCR were highest at 18 degrees C when compared to the other assay temperatures. However, at low and high extreme temperatures, i.e. at 12 and 40 degrees C, states III and IV respiration rates were not clearly distinguishable from each other indicating that mitochondria were completely uncoupled. Positive correlations were noticed between temperature and the levels of both lipid peroxidation and H2O2. It is inferred that fluctuations on either side of ambient habitat temperature may adversely influence mitochondria respiration and oxidative metabolism in S. serrata. The results provide baseline data to understand the impacts of acute changes in temperature on ectotherms inhabiting estuarine or marine environments. (C) 2014 Elsevier Ltd. All rights reserved.

Inhibition of Mycobacterium tuberculosis topoisomerase I by m-AMSA, a eukaryotic type II topoisomerase poison

m-AMSA, an established inhibitor of eukaryotic type II topoisomerases, exerts its cidal effect by binding to the enzyme-DNA complex thus inhibiting the DNA religation step. The molecule and its analogues have been successfully used as chemotherapeutic agents against different forms of cancer. After virtual screening using a homology model of the Mycobacterium tuberculosis topoisomerase I, we identified m-AMSA as a high scoring hit. We demonstrate that m-AMSA can inhibit the DNA relaxation activity of topoisomerase I from M. tuberculosis and Mycobacterium smegmatis. In a whole cell assay, m-AMSA inhibited the growth of both the mycobacteria. (C) 2014 Elsevier Inc. All rights reserved.

Estimation of the 2.0(5) helix type i -> i hydrogen bond energy at Aib*-Oxa motif: an isodesmic approach

Bending at the valence angle N-C-alpha-C' (tau) is a known control feature for attenuating the stability of the rare intramolecular hydrogen bonded pseudo five-membered ring C-5 structures, the so called 2.0(5) helices, at Aib. The competitive 3(10)-helical structures still predominate over the C5 structures at Aib for most values of tau. However at Aib*, a mimic of Aib where the carbonyl 0 of Aib is replaced with an imidate N (in 5,6-dihydro-4H-1,3-oxazine = Oxa), in the peptidomimic Piv-Pro-Aib*-Oxa (1), the C(5)i structure is persistent in both crystals and in solution. Here we show that the i -> i hydrogen bond energy is a more determinant control for the relative stability of the C5 structure and estimate its value to be 18.5 +/- 0.7 kJ/mol at Aib* in 1, through the computational isodesmic reaction approach, using two independent sets of theoretical isodesmic reactions. (C) 2014 Elsevier Ltd. All rights reserved.

Comparative Studies on the Bioremediation of Hexavalent and Trivalent Chromium using Citrobacter freundii: Part I-Effect of parameters controlling Biosorption

The potential of Citrobacter freundii, a Gram negative bacteria for the remediation of hexavalent chromium (Cr(VI)) and trivalent chromium (Cr(III))) from aqueous solutions was investigated. Bioremediation of Cr(VI) involved both biosorption and bioreduction processes, as compared to only biosorption process observed with respect to Cr(III) bioremediation. In the case of Cr(VI) bioremediation studies, about 59 % biosorption was achieved at an equilibrium time of 2 h, initial Cr(VI) concentration of 4 mg/L, pH 1 and a biomass loading of 5x10(11) cells/mL. The remainder, 41 %, was found to be in the form of Cr(111) ions owing to bioreduction of Cr(VI) by the bacteria resulting in the absence of Cr(VI) ions in the residue, there by meeting the USEPA specifications. Similar studies were carried out using Cr(III) solution for an equilibrium time of 2 h, Cr(III) concentration of 4 mg/L, pH 3 and a biomass loading of 6.3x10(11) cells/mL., wherein a maximum biosorption of about 30 % was achieved.

Effect of metal oxidation state on FRET: a Cu(I) silent but selectively Cu(II) responsive fluorescent reporter and its bioimaging applications

Copper(II) and copper(I) complexes of a newly designed and crystallographically characterized Schiff base (HL) derived from rhodamine hydrazide and cinnamaldehyde were isolated in pure form formulated as Cu(L)(NO3)] (L-Cu) (1) and Cu(HL)(CH3CN)(H2O)]ClO4 (HL-Cu) (2), and characterized by physicochemical and spectroscopic tools. Interestingly, complex 1 but not 2 offers red fluorescence in solution state, and eventually HL behaves as a Cu(II) ions selective FRET based fluorosensor in HEPES buffer (1 mM, acetonitrile-water: 1/5, v/v) at 25 degrees C at biological pH with almost no interference of other competitive ions. The dependency of the FRET process on the +2 oxidation state of copper has been nicely supported by exhaustive experimental studies comprising electronic, fluorimetric, NMR titration, and theoretical calculations. The sensing ability of HL has been evaluated by the LOD value towards Cu(II) ions (83.7 nM) and short responsive time (5-10 s). Even the discrimination of copper(I) and copper(II) has also been done using only UV-Vis spectroscopic study. The efficacy of this bio-friendly probe has been determined by employing HL to detect the intercellular distribution of Cu(II) ions in HeLa cells by developing image under fluorescence microscope.

Graded IR Filters: Distinguishing Between Single and Multipoint NO2 center dot center dot center dot I Halogen Bonded Supramolecular Synthons (P, Q, and R Synthons)

The NO2 center dot center dot center dot I supramolecular synthon is a halogen bonded recognition pattern that is present in the crystal structures of many compounds that contain these functional groups. These synthons have been previously distinguished as P, Q, and R types using topological and geometrical criteria. A five step IR spectroscopic sequence is proposed here to distinguish between these synthon types in solid samples. Sets of known compounds that contain the P, Q, and R synthons are first taken to develop IR spectroscopic identifiers for them. The identifiers are then used to create graded IR filters that sieve the synthons. These filters contain signatures of the individual NO2 center dot center dot center dot I synthons and may be applied to distinguish between P, Q, and R synthon varieties. They are also useful to identify synthons that are of a borderline character, synthons in disordered structures wherein the crystal structure in itself is not sufficient to distinguish synthon types, and in the identification of the NO2 center dot center dot center dot I synthons in compounds with unknown crystal structures. This study establishes clear differences for the three different geometries P, Q, and Rand in the chemical differences in the intermolecular interactions contained in the synthons. Our IR method can be conveniently employed when single crystals are not readily available also in high throughput analysis. It is possible that such identification may also be adopted as an input for crystal structure prediction analysis of compounds with unknown crystal structures.