An algorithmic characterization and spectral analysis of canonical splitting signed graph ξ(Σ).

An ordered pair Σ=(Σu,σ) is called the signed graph, where Σu=(V,E) is an underlying graph and σ is a signed mapping, called signature, from E to the sign set {+,-}. A marking of Σ is a function µ:V(Σ)→{+,-}. The canonical marking of a signed graph Σ, denoted µσ, is given as µσ(v)=Πvu∈E(Σ)σ(vu). The canonical splitting signed graphξ(Σ) of a signed graph Σ is defined as a signed graph ξ(Σ)=(V(ξ),E(ξ)) , with V(ξ)=V(Σ)∪V', where V'  is copy of a vertex set in V(Σ) s.t. for each vertex u∈V(Σ), take a new vertex u' and E(ξ) is defined as, join u' to all the vertices of Σ adjacent to u by negative edge if µσ(u)=µσ(v)=-, where v∈N(u) and by positive edge otherwise. The objective of this paper is to propose an algorithm for the generation of a canonical splitting signed graph, a splitting root signed graph from a given signed graph, provided it exists and to give the characterization of balanced canonical splitting signed graph. Additionally, we conduct a spectral analysis of the resulting graph. Spectral analysis is performed on the adjacency and Laplacian matrices of the canonical splitting signed graph to study its eigenvalues and eigenvectors. A relationship between the energy of the original signed graph Σ and the energy of the canonical splitting signed graph ξ(Σ) is established. •Algorithm to generate canonical splitting signed graph ξ(Σ).•Spectral Analysis is performed for both adjacency and Laplacian matrices of canonical splitting signed graph ξ(Σ).

Algorithmic approach to find S -consistency in Common-Edge signed graph.

Common-Edge signed graph C E ( S ) of a signed graph S is a signed graph whose vertex-set is the pairs of adjacent edges in S and two vertices are adjacent if the corresponding pairs of adjacent edges of S have exactly one edge in common, with the sign same as that of Common-Edge. S -Marked signed graph T is a signed graph which receives the marking µ due to the signed graph S called marker. Further, T is S -consistent if a marker S is defined and if S -marking µ of T with respect to which marked signed graph T µ is consistent. In this paper, we give an algorithm to detect if C E ( S ) is S -consistent or not and determine its complexity. • Algorithm to detect if C E ( S ) is S -consistent or not. • Determination of algorithm's complexity.

Study of biofilm formation in bacterial isolates from contact lens wearers.

Purpose: To detect biofilm forming capacity of bacterial isolates obtained from the conjunctiva, contact lens and accessories of contact lens wearers using phenotypic and genotypic methods. Methods: Bacterial strains were collected from the conjunctiva, contact lens and lens storage cases of contact lens wearers. The phenotypic detection of biofilm production was done using the tube method and congo red agar method. The biofilm-forming related genes, icaA, of Coagulase negative Staphylococcus (CONS) and Staphylococcus aureus, and pslA, of P. aeruginosa, were detected using PCR. Results: A total of 265 bacterial isolates which included S. aureus, CONS, Pseudomonas, Nil-fermenter Gram-negative bacilli (NFGNB), Bacillus spp, Diphtheroids, Micrococci, Klebsiella pneumonia, Klebsiella oxytoca, E. coli, Proteus mirabilis, Proteus vulgaris, Citrobacter koseri, Citrobacter freundii, Enterobacter cloacae, Moraxella were obtained. Of the 265 isolates, 53.5% were moderately positive, 33.2% strongly positive and 13.2% negative for biofilm production by tube method and 36.6% were moderately positive, 40% strongly positive and 23.3% negative for biofilm production by congo red agar method. Of the four S. aureus isolates, two (50%) showed the presence of icaA gene. Of the 23 CONS isolates, three (13%) showed the presence of icaA gene. All the Pseudomonas isolates were negative for presence pslA (1119 bp) gene though most of them were phenotypically positive for biofilm formation. Conclusion: Most of the bacterial isolates obtained from contact lens wearers had the potential to produce biofilms. Tube method and Congo red agar method exhibited significant statistical correlation (P-value = 0.006) and picked up a good number of biofilm-forming isolates, hence may be used for detection of biofilm production. The absence of biofilm-forming gene did not rule out the possibility for phenotypic biofilm production by bacteria.

Comparison of microbiome isolated from the conjunctiva, contact lens and lens storage case of symptomatic and asymptomatic contact lens users.

BACKGROUND AND OBJECTIVES: Contact lenses (CLs) are increasingly being used for cosmetic or therapeutic purposes. Lack of compliance and poor hygiene towards lens care is strongly associated with microbial contamination and has been proved to result in eye infections. The present study was done to compare the microbial flora between symptomatic and asymptomatic contact lens users. The study also attempts to analyze the contact lens hygiene practices of CL users. MATERIALS AND METHODS: Six samples each were collected from both the eyes, CLs and lens cases of 40 CL users (n=240) divided into two groups based on symptoms present asasymptomatic CL users and symptomatic CL users. Organisms were identified using standard microbiological techniques. RESULTS: The proportion GNB obtained in symptomatic CL users was significantly higher when compared to asymptomatic CL users (p-value= <0.003). In 56.2% eyes, the microbial flora of conjunctiva was similar to either the contact lens isolate/storage case. Enterococcal microbial keratitis was seen in one case. CONCLUSION: There was significant microbial contamination present in CL users despite compliance to contact lens hygiene practices. There were a significant number of bacteria (p-value <0.001) present which were resistant to ampicillin, amoxicillin-clavulanate, and cefotaxime in both the groups.

Characterization of 2-Path Product Signed Graphs with Its Properties.

A signed graph is a simple graph where each edge receives a sign positive or negative. Such graphs are mainly used in social sciences where individuals represent vertices friendly relation between them as a positive edge and enmity as a negative edge. In signed graphs, we define these relationships (edges) as of friendship ("+" edge) or hostility ("-" edge). A 2-path product signed graph [Formula: see text] of a signed graph S is defined as follows: the vertex set is the same as S and two vertices are adjacent if and only if there exists a path of length two between them in S. The sign of an edge is the product of marks of vertices in S where the mark of vertex u in S is the product of signs of all edges incident to the vertex. In this paper, we give a characterization of 2-path product signed graphs. Also, some other properties such as sign-compatibility and canonically-sign-compatibility of 2-path product signed graphs are discussed along with isomorphism and switching equivalence of this signed graph with 2-path signed graph.

Studies for development of novel quinazolinones: new biomarker for EGFR.

The binding capabilities of a series of novel quinazolinone molecules were established and stated in a comprehensive computational methodology as well as by in vitro analysis. The main focus of this work was to achieve more insight of the interactions with crystal structure of PDB ID: 1M17 and predict their binding mode to EGFR. Three molecules were screened for further examination, which were synthesized and characterized using spectroscopic techniques. The persuasive affinity of these molecules towards EGFR inhibition (IC50 for QT=45nM) was established and validated from specific kinase assay including the cell viability spectrophotometric assay (QT=12nM). Drug likeliness property were also considered by analysing, the ADME of these molecules by using scintigraphic techniques. The result showed antitumour activity of QT (4.17 tumour/muscle at 4h). Further photo physical properties were also analysed to see in vitro HSA binding to QT.

An Algorithm to detect balancing of iterated line sigraph.

A signedgraph (or sigraph in short) S is a graph G in which each edge x carries a value [Formula: see text] called its sign   denoted specially as [Formula: see text]. Given a sigraph S,  H = L(S)   called the line sigraph of S is that sigraph in which edges of S are represented as vertices, two of these vertices are defined to be adjacent whenever the corresponding edges in S have a vertex in common and any such edge ef is defined to be negative whenever both e and f are negative edges in S. Here S is called root sigraph of H. Iterated signed line graphs [Formula: see text] = [Formula: see text] k [Formula: see text] [Formula: see text], S:= [Formula: see text] is defined similarly. In this paper, we give an algorithm to obtain iterated line sigraph and detect for which value of 'k' it is balanced and determine its complexity. In the end we will propose a technique that will use adjacency matrix of S and adjacency matrix of [Formula: see text] which is balanced for some 'k' as a parameter to encrypt a network and forward the data in the form of balanced [Formula: see text] and will decrypt it by applying inverse matrix operations.

Synthesis, biological evaluation and molecular docking studies of high-affinity bone targeting N,N(') -bis (alendronate) diethylenetriamene-N,N'-triacetic acid: a bifunctional bone scintigraphy agent.

A bisphosphonate derivative DTPA-bis(alendronate) conjugate has been synthesized and evaluated as potential radiopharmaceutical for bone imaging. The compound was synthesized by the covalent coupling of DTPA-bis(anhydride) with alendronate and was char-acterized on the basis of IR, NMR and mass spectroscopy. It was labelled with (99m) Tc with 96% efficacy and was found stable for about 24 h under physiological conditions. Blood kinetic studies of (99m) Tc DTPA-bis(alendronate) showed a biexponential pattern as well as quick washout from the blood circulation. The biological t1/2 (F) and t1/2 (S) were found to be 50 min ± 0.001 and 6 h 30 min ± 0.005, respectively. Imaging and biodistribution studies showed a significant accumulation of (99m) Tc DTPA-bis(alendronate) conjugate at bone site. Bone-to-muscles ratios were 12.08 ± 0.001 at 1 h, 45.33 ± 0.001 at 4 h and 35.83 ± 0.001 at 24 h after post-injection, respectively. The receptor binding of the (99m) Tc-DTPA-bis (alendronate) was established on human bone cell line (Soas-2) revealed KD = 0.86 nm. The preliminary result of the (99m) Tc-DTPA-bis(alendronate) is encouraging to carrying out further in vivo experiment for targeted bone imaging because of good-bone-to-normal-organ contrast. Further docking analysis with molecular targets, farnesyl diphosphate synthase, geranylgeranyl pyrophosphate and osteocalcin revealed the high affinity of -17.419 and thus represents strong potential of bone-imaging agent.

Novel benzimidazole analogs as inhibitors of EGFR tyrosine kinase.

A series of new benzimidazole congeners were synthesized, and their structures were elucidated on the basis of elemental analyses and spectral studies (¹H NMR, FT-IR and EI-MS). Preliminary pharmacokinetic studies showed a promising outlook for further in vivo evaluation. The newly synthesized compounds were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. Most of the tested compounds exhibited antitumor activity with IC50 values in the micro to nano molar range.

Design and docking studies of [diethylenetriaminepentaacetic acid-(amino acid)2] with acetylcholine receptor as a molecular imaging agent for single-photon emission computed tomographic application.

The acetylcholine receptor is an essential link between the brain and the muscles, so it is a sensitive location for attack. In this study, some reversible [diethylenetriaminepentaacetic acid-(amino acid)2] have been docked computationally to the active site of the acetylcholine receptor. The induced fit method was employed to perform the automolecular docking for these systems. The result of docking studies generated thermodynamic properties, such as free energy of bindings (Glide score) and their weak electrostatic interactions. On the basis of these results, scintigraphic imaging studies were performed in mice. Among the radiotracers evaluated in this study, compound derived from 5-hydroxytryptophan/tryptophan exhibited remarkable localization in the brain, whereas radiotracer derived from l-histidine shows moderate accumulation in the brain. Preliminary studies with these amino acid-based ligands are encouraging to carrying out further in vivo experiments for targeted imaging.

Kinetics of formation for lanthanide (III) complexes of DTPA-(Me-Trp)2 used as imaging agent.

Diethlenetriamine-N,N,N'N''N''-pentaacetic acid (DTPA)-bis (amide) analogs have been synthesized and evaluated as a potential biomedical imaging agents. Imaging and biodistribution studies were performed in mice that showed a significant accumulation of DTPA analogs in brain. The stability and protonation constants of the complexes formed between the ligand [DTPA-(Me-Trp)(2)] and Gd(3+), Eu(3+), and Cu(2+) have been determined by pH potentiometry (Gd(3+), Eu(3+)) and spectrophotometry (Cu(2+)) at 25 °C and at constant ionic strength maintained by 0.10 M KCl. The kinetic inertness of Gd [DTPA-(Me-Trp)(2)] was characterized by the rates of exchange reactions with Zn(2+) and Eu(3+). In the Eu(3+) exchange, a second-order [H(+)] dependence was found for the pseudo-first-order rate constant [k(0) = (4.5 ± 1.2) × 10(-6)/s; k(1) = 0.58 ± 0.1 /M/s, k(2) = (6.6 ± 0.2) × 10(4) /M(2)/s, k(3) = (4.8 ± 0.8) × 10(-4) /M/s]. In the Eu(3+) exchange, at pH <5.0, the rate decreases with increasing concentration of the exchanging ion. At physiological pH, the kinetic inertness of [DTPA-(Me-Trp)(2)] is more inert than GdDTPA(2-), the most commonly used MRI contrast agent (t(1/2) = 127 h). High kinetic stability is an important requirement for the Gd complexes used as contrast enhancement agents in magnetic resonance imaging.

Quantitative structure-activity relationship analysis of 4(3H)-quinazolone derivatives as tyrosine kinase inhibitors by multiple linear regression.

Computational chemistry is playing an increasingly important role in drug design and discovery, structural biology, and quantitative structure-activity relationship studies. A series of 4(3H)-quinozolone derivatives were screened for two-dimensional quantitative structure-activity relationship studies and subsequently their absorption, distribution, metabolism, and excretion (ADME) properties with the use of soft modeling techniques after selecting suitable descriptors for molecular structure. Multiple linear regression analysis was performed for this study. The final quantitative structure-property relationship mathematical models were found as follows: Equation [Y= log (1MIC)] [symbol: see the text] pMIC= 1. 0:2165κ(1) - 2.082χ(3) - 0.3235µT - 0.2185µx - 100.6qN - 35.42. 2. 0:2185κ(1) - 2.1575χ(3) - 0.3622µT - 0.2142µx - 100.4qN - 31.25. 3. 0:0015ω - 2.0822χ(3) - 0.1252µT - 0.2180µx - 112.9qN - 36.05. 4. 2:108χ(3) - 0.0035ET - 0.2033µx - 3.489qesp - 92.60qN - 33.20. 5. 0:2140κ(1) - 2.186χ(3) - 0.0036Oxxx - 0.0016Oxyy - 78.02qN - 31.52.

Synthesis and biological evaluation of (99m)Tc-DTPA-bis(His) as a potential probe for tumor imaging with SPECT.

(99m)Tc-DTPA-bis(His) conjugate has been synthesized and evaluated as a potential radiopharmaceutical for tumor imaging. The compound was synthesized by the covalent coupling of DTPA bis(anhydride) with L-histidine and was characterized on the basis of infrared, nuclear magnetic resonance, and mass spectroscopy. (99m)Tc-labeled compound was found stable for about 24 hour under physiologic conditions with a more than 96% radiolabeling yield. A blood kinetic study of this complex showed a biexponential pattern as well as quick washout from the blood circulation. The biologic t(1/2)(F) and t(1/2)(S) was found to be 45 +/- 0.041 minutes and 6.5 hours +/- 0.039 minutes, respectively. Imaging and biodistribution studies were performed in mice bearing Ehrlich ascites tumor (EAT) tumors in the right thigh. The EAT tumors in the mice were readily visible in the gamma-images and showed major accumulation of the radiotracer in the kidney. Biodistribution studies revealed a high accumulation at the tumor site. Tumor-to-muscle ratios were 5.07 +/- 0.08 and 4.2 +/- 0.01 at 1 and 4 hours, respectively. The receptor binding of the (99m)Tc-DTPA-bis(His) by an established human tumor cell line (U87-MG) showed K(D) = 1.08 nM. The preliminary studies of the (99m)Tc-DTPA-bis(His) are encouraging to carrying out further in vivo experiments for targeted tumor imaging.

99mTc-DTPA-amino acids conjugate as specific SPECT pharmaceuticals for tumor imaging.

(99m)Tc-Diethylene triamine pentaacetic acid-bis (amide) conjugates have been synthesized and evaluated as a potential radiopharmaceutical for tumor imaging. The compounds were synthesized by the condensation reaction of DTPA bis(anhydride) with different l-amino acids (methyl tryptophan, and 5-hydroxy tryptophan) and were characterized on the basis of IR, NMR, and Mass spectroscopy. (99m)Tc-labeled compounds were found stable for about 24 h under physiological conditions with more than 95% radiolabeling yield. Blood kinetic studies of all these complexes showed a bi-exponential pattern as well as quick wash out from the blood circulation. The biological t(1/2)(F) and t(1/2)(S) were found to be 20 +/- 0.001 min for DTPA-(Me-Trp)(2) and 18 +/- 0.001 min for DTPA-(5HT)(2) and t(1/2) (slow) 5 h 45 min +/- 0.001, 5 h 30 +/- 0.001 min for DTPA-(Me-Trp)(2), and DTPA-(5HT)(2), respectively. Imaging and biodistribution studies were performed in mice bearing Ehrlich ascites tumor (EAT) tumors in right thigh. Radioconjugate derived from l-5-hydroxytryptophan exhibited remarkable localization at tumor site; whereas radiotracer derived from l-methyl tryptophan shows relatively less accumulation at the tumor site. Tumor-to-muscles ratios were 5.07 +/- 0.001, and 4.2 +/- 0.001 at 1 and 4 h for (99m)Tc-DTPA-(Me trp)(2) and 4.97 +/- 0.001 and 5.8 +/- 0.001 at 1 and 4 h after postinjection for (99m)Tc-DTPA-(5HT)(2), respectively. The preliminary results with these amino acid based ligands are encouraging to carrying out further in vivo experiments for targeted tumor imaging.

Synthesis and assessment of 99mTc chelate-conjugated alendronate for development of specific radiopharmaceuticals.

Indole-based alendronate (AI) was derived from the condensation reaction of indole 3-carboxaldehyde with sodium alendronate (ALN) and was characterized by various spectroscopic methods (e.g., ultraviolet, fourier-transform-infrared, and liquid chromatography mass spectrometry). The AI was labeled with (99m)Tc and radiochemical purity was above 97%, which was ascertained by instant thin-layer chromatography, using different solvent conditions, with a specific activity 2-5 mCi/mg. The receptor ligand assay on human bone cell line Soas-2 showed K(D) = 0.55 nM. The derivative (AI) was stable, which was determined under physiologic conditions up to 24 hours The blood kinetic study showed a biexponential pattern as well as quick wash-out from the circulation with varying biologic t(1/2)(F) and t(1/2)(S). Excellent-quality radio images were recorded of bone, showing a rapid clearance of background activity, at an early visualization at 1.5 hours. The excretory pathway of the derivative was through the kidneys, which was evidenced by biodistribution studies. Thus, the newly synthesized derivative can be considered as a specific bone-seeking agent.

Polyethylene glycol conjugates of methotrexate and melphalan: synthesis, radiolabeling and biologic studies.

Polyethylene glycols (PEGs) are potential drug carriers for humanizing the therapeutic index of anti-cancer agents. In this paper, we report on the modification of the anticancer drugs, methotrexate (MTX) and melphalan (L-PAM), covalently linked to PEGs for drug delivery. Conjugates of MTX and L-PAM were analyzed through different spectroscopic techniques. Both conjugates were labeled with (99m)Tc by the classical way, using reducing agents at a physiologic pH. Blood kinetic data revealed the biphasic pattern of clearance. Evaluation of the in vitro cytotoxicity of the drug polymer conjugates on the U87MG human glioma cell line revealed that the conjugates showed enhanced dose-dependent cytotoxicity.

Synthesis, characterization and biological activity of Schiff base analogues of indole-3-carboxaldehyde.

Eight novel heterocyclic Schiff bases derived from the condensation reactions of indole 3-carboxaldehyde with different l-amino acids (histidine, glutamic acid, aspartic acid, leucine, valine) as well as with some aminophenols, have been synthesized and characterized by various spectroscopic methods (IR, MS, (1)H NMR). Schiff base derivatives of indole 3-carboxaldehyde were labeled with (99m)Tc and radiochemical purity was above 97% which is ascertained by instant thin layer chromatography using different solvent conditions. Stability studies of all the derivatives of indole 3-carboxaldehyde was determined under physiological conditions and were stable for more than 24h. Blood clearance showed a quick wash out from the circulation and biological half life was found to be t((1/2))(F)=1h 15min; t((1/2))(S)=10h 05min. Excellent quality radioimages of tumor bearing mice were recorded showing rapid clearance of background activity, visualization of tumor at 3h and clearance from kidneys of histidine analogue which was further evidenced in biodistribution studies. Antimicrobial activity of these Schiff base compounds was evaluated against Bacillus subtilis, Pseudomonas fluorescence, Staphylococcus aureus, Aspergillus niger, Candida albicans and Trichophyton rubrum.

Synthesis and evaluation of novel benzimidazole derivative [Bz-Im] and its radio/biological studies.

Two different benzimidazole analogues act as multimodal agent, first one as novel non-peptidic CCK-B receptor antagonist and similarly as potent anti-fungal agent, designated as [Bz-Im]. These compounds were synthesized and characterized by spectroscopic techniques such as FT-IR, NMR, EI-MS and also evaluated for specific radiopharmaceuticals. Preliminary radiolabeling results with (99m)Tc and biological evaluation studies showed promising results for further evaluation in vivo. The efficiency of labeling was more than 97% and complex was stable for about 12h at 30 degrees C in the presence of serum. Both ligands showed binding to most of the organs, known to express CCK receptors in biodistribution studies. Cholecystokinin (CCK(1) andCCK(2)) receptor binding affinities of these analogues are, IC(50), 0.942+/-0.107 for compound C and 0.665+/-0.211 for compound D in rat pancreatic acini. The anti-fungal activity has shown inhibitory activity against Aspergillus flavus and Aspergillus niger. These studies have provided a new template for further development of non-peptidic ligands for diagnostic and therapeutic purposes of diseases related with CCK receptors as well as anti-microbes.