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Background Staphylococcus aureus is one of the commensal bacteria and components of nose normal flora in 30–40% of people. The cellular phone is infected through the hands of a person who has already been infected with nasal discharge, in the hospital. Patients and family members with a weakened immune system are at high risk of contamination; the treatment procedure is difficult. Materials and methods 200 individuals who were working in the emergency departments of Ghaem were included in the study. Sampling was done by three sterile swabs; two swabs from the nose and one from the surface of the cellular phone. The diagnosis was done according to the staphylococcus biochemical tests. Beta-lactamase positive staphylococcus was identified by nitrocefin. MIC method was performed using E-test strips and agar dilution for detecting the MRSA. Results 86 out of 200 nasal, and 200 cellular phone samples were diagnosed as beta-lactamase positive staphylococci and sensitivity test was done. 17 out of 86 beta-lactamase positive Staphylococcus aureus samples were resistant to cefoxitin, piperacillin, ceftriaxone, and cefotaxime; just one of these 17 samples was resistant to vancomycin. 24 samples were contaminated with healthcare-associated MRSA (HA-MRSA). Totally, cellular phone and nasal discharge of 12% of studied individuals were infected with the HA-MRSA. Conclusion Cell phone usage should be prohibited in the hospital sections. Disinfection of the mobile phone should be taken when leaving the hospital, along with hand, face, and nose washing seriously. It is suggested to evaluate all persons working in hospitals regarding the contamination to MRSA.

This paper addresses the problem of executing multiple prioritized tasks for robot manipulators with compliant behavior in the remaining null space. A novel controller–observer is proposed to ensure accurate accomplishment of various tasks based on a predefined hierarchy using a new priority assignment approach. Force control, position control and orientation control are considered. Moreover, a compliant behavior is imposed in the null space to handle physical interaction without using joint torque measurements. Asymptotic stability of the task space error and external torque estimation error during executing multiple tasks are shown. The performance of the proposed approach is evaluated on a 7R light weight robot arm by several case studies.

In this paper the attitude control of a spacecraft simulator using Reaction Wheels (RW) as the actuators is investigated. The main goal of the current study is to bring the RWs to the rest at the end of the maneuver without angular velocity measurement. A modified feedback linearization controller is applied by considering the Euler angles of the simulator as the output and the RWs angular momentums as the internal state variables. The stability of the proposed controller and the internal dynamics is analyzed using Lyapunov theory. Two modified sliding mode observers are designed to estimate the angular velocities of the spacecraft attitude control subsystem simulator. The proposed observers do not use the control input and the detailed knowledge of the model and thus it can be implemented easily. The global stability of the system is proved. The proposed controller and observers are finally evaluated numerically and experimentally on an attitude spacecraft simulator.

The interaction between ofloxacin (Oflx) and calf thymus DNA (ct DNA) in the presence and absence of histone H1 was investigated in Tris buffer (pH=6.8) using UV–vis absorption and fluorescence spectroscopy, as well as resonance light scattering (RLS), transition temperature, circular dichroism (CD), viscosity and molecular modeling techniques. The results indicated that H1 induced changes in the binding affinity between Oflx to ct DNA and that the major binding mode was intercalative binding. The RLS results implied changes in particle size and induced structural changes of the ct DNA-Oflx complex in the presence of H1 as a ternary system as opposed to as a binary system. The binding constant, Ksv, and the number of binding sites, n, of ct DNA-Oflx in the presence of H1 were obtained by fluorescence quenching that showed a static quenching behavior of the complex formation in the ternary system. The Ksv values of H1-Oflx, ct DNA-Oflx and (ct DNA-H1) Oflx were (9.86 ±0.6) × 107 M-1, (9.08 ± 0.4) × 107 M-1 and (4.13 ± 0.3) × 107 M-1 respectively. The Ksv values showedkey role of H1 in binding affinity of Oflx to ct DNA that caused the different of interaction behaviorbetween ct DNA and Oflx in the presence of H1. The thermodynamic parameters were calculated from the fluorescence data measured at three different temperatures, and showed that the binding of Oflx to the ct DNA-H1 complex was driven mainly by hydrogen bonding and van der Waals forces. The CD technique demonstrated that, in the presence of H1, the ellipticity values of the ct DNA-Oflx complex changed, which gave rise to a different chirality of ct DNA-Oflx induced by H1. Viscosity measurements revealed that the specific viscosity of ct DNA increased with the Oflx concentration in the absence and presence of H1. Different curves confirmed that Oflx bound to ct DNA with varying affinities in the absence and presence of H1. Molecular modeling confirmed the experimental results regarding the binding of Oflx to ct DNA in the absence and presence of H1.

In recent years, abuse of synthetic cathinones, in particular, mephedrone, has increased among young adults worldwide. The study aim is to investigate the effects of mephedrone exposure during the gestational period on mice offspring outcomes, focusing on hippocampal neurotoxicity. The pregnant mice received mephedrone (50 mg/kg, sc) on a regular schedule (once daily on all days, from day 5 to 18 of gestation) or repeated schedule (thrice daily on day 5, 6, 11, 12, 17, and 18 of gestation) to simulate regular or recreational use of mephedrone, respectively. Results showed that the percentage of weight gain in pregnant mice was significantly lower in both regular and repeated schedule mephedrone groups (p 0.01). Also, mephedrone significantly reduced the number and weight of delivered pups and increased the rate of stillbirth (p 0.05). Immunohistochemistry and TUNEL assay showed an inhibition of cell proliferation (p 0.05) and an increase of apoptosis (p 0.05) in the hippocampus of delivered pups of the repeated schedule mephedrone group. This apoptotic effect was associated with enhanced expression of the pro-apoptotic Bax gene (p 0.05) and reduction of expression of the anti-apoptotic Bcl-2 gene (p 0.05) as evaluated by real-time PCR. The Morris water maze showed an impairment of spatial learning (p 0.05) and reference memory (p 0.01) in offspring born from litters exposed to mephedrone (repeated schedule). In conclusion, the present study has shown that regular and repeated exposure to mephedrone during the gestational period increases the risk of low birth weight and stillbirth. Also, repeated use of mephedrone impairs learning and memory processes through hippocampal damage.

In this paper, the Intelligent Impedance Control based Wavelet Neural Network (IIC-WNN) is introduced as a noble adaptive variable impedance approach to enhance the efficiency of tracking the desired force and interaction with varying unknown (in terms of unknown stiffness and unknown geometric) environment. In the proposed method, a systematic online adaptation mechanism using the wavelet neural network is presented to adapt the impedance parameter according to a variable environment. Using the introduced adaptive law, the robot would be able to track the desired force on the moving environment with the unknown stiffness. Unlike the general impedance control which the position and stiffness of the environment need to be available and known for choosing the impedance parameters, the proposed structure for the impedance equation leads to adapt the impedance parameters according to the interaction environment. In addition, the stability conditions and adaptation laws using Lyapunov’s method for the variable impedance are given to guarantee the force tracking and stability of the closed-loop system. Finally, various numerical and experimental results verify the performance of the proposed adaptive approach. The experimental results strongly prove that the presented method has a better force tracking performance than the general impedance with constant parameters.

In order to prevent spreading of Mycobacterium tuberculosis (Mtb), it is necessary to discover effective vaccines, fast and reliable diagnosis, and appropriate treatment schemes. In the present study, an Fc-tagged recombinant Mtb–ESAT-6 was produced to make a selective delivery system for promoting cellular immunity. To determine 3D structure of the recombinant protein, model building was performed in MODELLER9v13 program. After preparation of Mtb–DNA and Fcγ1 cDNA, they were amplified by specific primers to make ESAT-6 and Fcγ1 products to fuse them in frame using splicing by overlap extension (SOEing)-PCR. After TA cloning, the construct was sequenced to confirm no errors have been introduced. The recombinant DNA was then subcloned into PDR2EF1α eukaryotic expression vector. The plasmid sequenced over the sites at which two DNA fragments were cloned to ensure that the ligation had generated an in-frame fusion of the genes. The CHO cells were then stably transected by PDR2EF1α–ESAT-6:Fcγ1 vector using lipofectamin and the expression and its binding to the Fcγ receptor (FcγRI) on APCs were confirmed by immunofluorescence assay (IFA). The IFA results demonstrated that ESAT6:Fcγ1 was expressed in engineered CHO cells. Semi-scale protein production and purification using HiTrap-PA column showed a high secretion of the recombinant protein by Western blotting method. The molecular weight of the monomer in the SDS-PAGE was equal to a protein of 50 kDa, which dimerizes by disulfide bond of Fcγ fragments. Since, ESAT6:Fcγ1 protein dimerizes and bind to FcγRs, therefore, Fc-tagged protein could target APCs for inducing appropriate immune response or using in interferon-based assays.

In this paper, a novel observer-based force control scheme is proposed to guarantee the position and force tracking in nonlinear teleoperation systems, subject to constant communication time delay. Stability of the teleoperation system is analytically proved using the Lyapunov stability theorem. Enough condition for asymptotic convergence of the force and position are derived. The transparency is also improved by force tracking capability of the system. The teleoperation controller is then applied to a pair of planar 2-DOF robots, connected via a communication channel with constant time delay. The experimental and simulation results demonstrate the effectiveness of the proposed control algorithm, in force estimation and dealing with time delay.

In this paper the effect of different parameters on the periodic orbits of an under-actuated passive biped is studied. The system is designed to follow a periodic orbit in the phase plane, starting from an initial condition and walking down a slope. The dynamic motion of the system is cast as an optimization problem under constraints that impose the periodicity with optimal behavior. The effect of dynamics and kinematics factors such as inertia and length characteristics of the biped and slope angle on the stability and bifurcation phenomena is extensively studied. In the following, it is shown how an under-actuated arm can perfectly synchronize its stabilizing motion with walking. The effect of dynamics parameters of the arm on the locomotion of the biped, stability criteria and the robustness of the whole system is extensively investigated. The results of the paper clearly illustrate the effects of dynamics parameters as well as the stabilizing arm on the stability, energy, and step characteristics of locomotion.

Cervical cancer remains one of the greatest life threatening diseases for women worldwide. Although chemotherapy is considered as a standard treatment for advanced cervical cancers, there are still some drawbacks in this procedure including side effects and acquired drug resistance, which necessitate further research on development of more effective agents with less side effects. Among natural compounds, coumarin derivatives have shown anticancer properties on various cancerous cells and coumarin ring has proven to have a paramount role in development of anticancer drugs. Here, we aimed to establish the structure-activity relationships of eighteen O-prenylated coumarin derivatives and determined their anticancer properties on HeLa cervical cancer and HDF normal cells by MTT assay. Moreover, the mechanism of cell death induced by these compounds and their effects on cell cycle were studied using flow cytometry. MTT results indicated that twelve O-prenylated coumarin derivatives exhibited selective toxicity on HeLa cells, while they had no significant toxic effects on normal cells. Besides, flow cytometric analyses, showed that the selected compounds induced apoptosis in HeLa cells, and could also result to G1 cell cycle arrest. In conclusion, analyzing structural-activity relationships revealed that a prenylation substitution at position 6 of the coumarin ring greatly improved anticancer properties of these agents. As these derivatives exerted their cytotoxic effects via apoptosis and were not toxic on normal cells, they can be considered as effective anticancer agents for further preclinical experiments.

A passivity-based control of Vertical Take-off and Landing (VToL) Unmanned Aerial Vehicles (UAVs) is presented in this paper. An estimator of unmodeled dynamics and external wrench (forces plus moments) acting on the aerial vehicle and based on the momentum of the system is employed to compensate such disturbances effects. This arrangement allows VToL UAVs to perform hovering, tracking and aerial manipulation tasks in unstructured environments. A rigorous stability proof is provided under certain assumptions. Experiments are presented to evaluate the performance of the proposed control design. Passivity-based framework is employed within a classical control scheme for UAVs.Control of angular dynamics does not rely upon exact model cancellation.Estimation is directly fed back to the passivity-based controller.Theoretical proofs and experiments are presented to validate the approach.

Kaposi׳s sarcoma-associated herpesvirus (KSHV) vOX2 is a cell surface glycoprotein expressed during viral lytic replication to suppress host inflammatory reactions. Here we have characterised vOX2 with biochemical, biophysical and bioinformatics tools and as a result propose a 3-dimensional model for vOX2 based on structural and functional homology with the PD-L1 protein. To validate this model, vOX2 was characterised by analytical ultracentrifugation (AUC) and circular dichroism spectroscopy (CD). The results identified the potential glycosylation sites and revealed that vOX2 is predominantly a beta-folded molecule with an RGD adhesion motif exposed on the C-terminal domain. The protein exists in monomer–dimer equilibrium similar to its IgV-type folded homologues, with 30–36% glycosylation and the molecular weight of the extracellular fragment of molecule is 32.0–33.6 kDa, much less than 50 kDa. Thus, the structural similarity to PD-L1 verifies its immunomodulatory potential and the RGD motif suggests an adhesive capacity.

In this work 4-amino-6-aryl-2-phenyl pyrimidine-5-carbonitrile derivatives were synthesized through a one-pot, three-component reaction of an aldehyde, malononitrile and benzamidine hydrochloride, in the presence of magnetic nano Fe3O4 particles as a catalyst under solvent-free conditions. 3-Amino-6-aryl-2-phenylpyrazolo[3,4-d]pyrimidine derivatives were prepared through an efficient and environmentally friendly reaction between 4-amino-6-aryl-2-phenylpyrimidine-5-carbonitrile derivatives and hydrazine hydrate and their antibacterial activity has been evaluated.

A series of 4,5-diaryl-1H-imidazole-2(3H)-thione was synthesized and their inhibitory potency against soybean 15-lipoxygenase and free radical scavenging activities were determined. Compound 11 showed the best IC(50) for 15-LOX inhibition (IC(50) = 4.7 μM) and free radical scavenging activity (IC(50) = 14 μM). Methylation of SH at C(2) position of imidazole has dramatically decreased the 15-LOX inhibition and radical scavenging activity as it can be observed in the inactive compound 14 (IC(50) >250 μM). Structure activity similarity (SAS) showed that the most important chemical modification in this series was methylation of SH group and Docking studies revealed a proper orientation for SH group towards Fe core of the 15-LOX active site. Therefore it was concluded that iron chelating could be a possible mechanism for enzyme inhibition in this series of compounds.

15-Lipoxygenases are one of the nonheme iron-containing proteins with ability of unsaturated lipid peroxidation in animals and plants. The critical role of the enzymes in formation of inflammations, sensitivities and some of cancers has been demonstrated in mammalians. Importance of the 15-lipoxygenases leads to development of mechanistic studies, products analysis and synthesis of their inhibitors. In this work new series of the 3-allyl-4-allyoxyaniline amides and 3-allyl-4-prenyloxyaniline amides were designed, synthesized and their inhibitory potency against soybean 15-lipoxygenase were determined. Among the synthetic amides, 3-allyl-4-(farnesyloxy)-adamantanilide showed the most potent inhibitory activity by IC 50 value of 0.69 μM. SAR studies showed that in spite of prenyl length increases, the effects of the amide size and its electronic properties on the inhibitory potency became predominant. The SAR studies was also showed that the orientation of allyl and prenyloxy moieties toward Fe core of the SLO active site pocket is the most suitable location for enzyme inhibition.

The impedance control of dual-arm 7-DOF cooperative manipulators is considered in this paper. Global compliant behavior for the whole system is achieved using impedance at three levels, i.e. object, end-effector and body level. A centralized impedance control strategy is provided to confer a compliant behavior to the object, while an active decentralized impedance control with force tracking is enforced to the end-effectors to control the internal forces on the object. A compliant behavior for the body of the dual-arm system is obtained by means of null-space impedance control. The manipulability measure of the whole system is locally maximized within this algorithm. The developed control scheme is verified in a simulation environment composed of two cooperating 7-DOF KUKA lightweight arms carrying a common object.

In the present study, a novel electrode based on 2,9-dihydroxy-1,10-diphenoxy-4,7-dithiadecane (DHDPDTD) that is selective to cerium (III) cations was evaluated electrochemically, and a Nerenstian slope (19.3 ± 1 mV decade−1) over a concentration range of 1.0 × 10−8–1.0 × 10−1 M and a detection limit of 2.1 × 10−9 M were observed. The proposed electrochemical sensor displayed a rapid response time of 10 s, improved selectivity towards Ce (III) cations in the presence of alkali, alkaline earth, transition and heavy metal cations, and could be used in a pH range of 5.0–8.0. Additionally, the proposed sensor was used as an indicator in the potentiometric titration of fluoride and the determination of F− ions in real samples.

A new series of amphiphilic β-cyclodextrins were designed and synthesized by grafting peptide chains on to all primary hydroxyl groups via ester bond formation. The desired amphiphilic structures have been produced from ester connection between the C-6 of β-cyclodextrin and the carboxyl group of N-acetylated resides: H2N–Leu–COOH, H2N–Leu-Gly–COOH, H2N–Leu-Gly-Leu–COOH, and H2N–Leu-Gly-Leu-Gly–COOH (3a–d). The synthetic pathway involves selective bromination of all primary hydroxyls of β-cyclodextrins and then substitution with the carboxylate moiety of the mentioned N-acetyl residues in the presence of DBU (1,8-diazabicyclo[5,4,0]undec-7-ene). The ability of the synthetic compounds for extraction and phase transfer of glucosamine, as a hydrophilic organic compound, was then studied. The results showed a considerable ability of these amphiphilic compounds for extraction and a selective tendency of 3c for phase transfer of glucosamine.

Selective PDE3 (phosphodiesterase 3) inhibitors improve cardiac contractility and may be used in congestive heart failure. However, their proarrhythmic potential is the most important side effect. In this work ten new synthetic compounds (3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methylbenzamide analogs: 4a-j) were designed, synthesized and tested for the inhibitory activity against human PDE3A and PDE3B. The strategy of the design was based on the structure of vesnarinone (a selective PDE3 inhibitor) and its docking analysis results. The synthetic compounds showed better PDE3 inhibitory activity in comparison with vesnarinone. Using docking analysis, a common binding model of each compound toward PDE3 was suggested. In the next step the potential cardiotonic activity of the best PDE3A inhibitors (4b, IC(50)=0.43+/-0.04microM) was evaluated by using the spontaneously beating atria model. In the experiment, atrium of reserpine-treated rat was isolated and the contractile and chronotropic effects of the synthetic compound were assessed. That was carried out in comparison with vesnarinone. The best pharmacological profile was obtained for the compound 4b, which displayed selectivity for increasing the force of contraction (46+/-3% change over the control) rather than the frequency rate (16+/-4% change over the control) at 100microM.

A group of 4-methoxyphenylacetic acid esters were designed, synthesized and evaluated as potential inhibitors of soybean 15-lipoxygenase (SLO) on the basis of eugenol and esteragol structures. Compounds 7d-e showed the best IC(50) in SLO inhibition (IC(50)=3.8 and 1.9 microM, respectively). All compounds were docked in SLO active site and showed that carbonyl group of compounds is oriented toward the Fe(III)-OH moiety in the active site of enzyme and fixed by hydrogen bonding with hydroxyl group. It is assumed that lipophilic interaction of ligand-enzyme would be in charge of inhibiting the enzyme activity. The selectivity of the synthetic esters in inhibiting of 15-HLOb was also compared with 15-HLOa by molecular modeling and multiple alignment techniques.

A group of 4-allyloxyaniline amides 5a-o were designed, synthesized and evaluated as potential inhibitors of soybean 15-lipoxygenase (SLO) on the basis of eugenol and esteragol structures. Compound 5e showed the best IC(50) in SLO inhibition (IC(50)=0.67+/-0.06 microM). All compounds were docked in SLO active site retrieved from RCSB Protein Data Bank (PDB entry: 1IK3) and showed that allyloxy group of compounds is oriented towards the Fe(3+)-OH moiety in the active site of enzyme and fixed by hydrogen bonding with two conserved His(513) and Gln(716). It is resulted that molecular volume of the amide moiety would be a major factor in inhibitory potency variation of the synthetic amides, where the hydrogen bonding of the amide group could also involve in the activity of the inhibitors.

A group of 4-allyl-2-methoxyphenol (eugenol) esters were designed, synthesized, and evaluated as potential inhibitors of soybean 15-lipoxygenase (SLO). Compounds 4c , 4d 4f , 4p , and 4q showed the best IC 50 in SLO inhibition (IC 50 = 1.7, 2.3, 2.1, 2.2, and 0.017 μM, respectively). All compounds were docked into SLO active site and showed that allyl group of compounds is oriented toward the iron atom in the active site of SLO. It is assumed that lipophilic interaction of ligand-enzyme would be in charge of inhibiting the enzyme activity. The selectivity of eugenol derivatives in inhibiting 15-HLOb was also compared with 15-HLOa by molecular modeling and multiple alignment techniques.

A group of 2-substituted pyrimido[4,5-b][1,4]benzothiazines were designed, synthesized, and evaluated as potential inhibitors of 15-lipoxygenase (15-LO). Compounds 4d and 4e showed the best IC50 of 15-LO inhibition (IC50=18 and 34 microM, respectively). All compounds were docked into 15-LO. As a result the sulfur atom was oriented toward the iron atom of the active site of 15-LO. We suggest the interaction of the iron atom is essential for the activity of the inhibitors.

Introduction: KSHV which is the etiological agent of Kaposi's Sarcoma encodes a protein by open reading frame (ORF) K14, called vOX2. This protein shares identity with the mammalian OX2 (CD200). Signal delivery of vOX2 occurs through binding to CD200R which contributes to maintaining the homeostasis of immune responses, in a manner similar to CTLA-4 and PDL-1/-2. Due to highly glycosylation and adhesive properties of vOX2, it failed to determine the 3D-structure of the protein by Xray crystallography method. Therefore, probable crystal structure of vOX2 has been bioinformatically identified. Material and methods: In order to identify the templates, BLAST sequence homology searches (NCBI) were performed. The PD-L1 (PDB entry: 3FN3) was chosen for modeling. Multiple alignment process was carried out on the selected sequences by ClustalX2 (protein weight matrix: BLOSUM series). Model building was performed in the program MODELLER9v5 using model-ligand algorithm and models at various refinement levels were generated. Finally the refined structures were minimized under molecular mechanic AMBER method (RMS gradient = 0.5) in HyperChem7.5. All models were validated using the program ERRAT and PROCHECK at UCLA. Results: The best 3D model had an Errat score of 94%. In the modelled protein all of the glycosyl-linked residues (Asn 83, 91, 138, 157 and 166) are situated in the external region of the 3D structure with steric flexibility of their side chains. Conclusion: Our modeling supports the data which indicates that vOX2 has two Ig-like domains, located between residue 9 to 120, and 130–160, respectively and the integrin-binding motif, RGD, at residues 190–193 is exposed.

Corrigendum Corrigendum to ‘‘Design, synthesis and SAR studies of 4-allyoxyaniline amides as potent 15-lipoxygensae inhibitors” [Bioorg. Med. Chem. 17 (2009) 1614] Seyed Mohammad Seyedi *, Hossein Eshghi , Zeinab Jafari , Neda Attaran , Hamid Sadeghian , Mohammad Reza Saberi , Mohammad Mahdi Riazi a Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad 917751436, Islamic Republic of Iran b School of Pharmacy, Pharmaceutical Research Center, Mashhad University of Medical Sciences, BuAli Square, Mashhad 9196773117, Islamic Republic of Iran