PAMAM Dendrimer-Drug Interactions: Effect of pH on the Binding and Release Pattern

Understanding the dendrimer-drug interaction is of great importance to design and optimize the dendrimer-based drug delivery system. Using atomistic molecular dynamics (MD) simulations, we have analyzed the release pattern of four ligands (two soluble drugs, namely, salicylic acid (Sal), L-alanine (Ala), and two insoluble drugs, namely, phenylbutazone (Pbz) and primidone (Prim)), which were initially encapsulated inside the ethylenediamine (EDA) cored polyamidoamine (PAMAM) dendrimer using the docking method. We have computed the potential of mean force (PMF) variation with generation 5 (G5)-PAMAM dendrimer complexed with drug molecules using umbrella sampling. From our calculated PMF values, we observe that soluble drugs (Sal and Ala) have lower energy barriers than insoluble drugs (Pbz and Prim). The order of ease of release pattern for these drugs from G5 protonated PAMAM dendrimer was found to be Ala > Sal > Prim > Pbz. In the case of insoluble drugs (Prim and Pbz), because of larger size, we observe much nonpolar contribution, and thus, their larger energy barriers can be reasoned to van der Waals contribution. From the hydrogen bonding analysis of the four PAMAM drug complexes under study, we found intermolecular hydrogen bonding to show less significant contribution to the free energy barrier. Another interesting feature appears while calculating the PMF profile of G5NP (nonprotonated)-PAMAM Pbz and G5NP (nonprotonated)-PAMAM-Sal complex. The PMF was found to be less when the drug is bound to nonprotonated dendrimer compared to the protonated dendrimer. Our results suggest that encapsulation of the drug molecule into the host PAMAM dendrimer should be carried out at higher pH values (near pH 10). When such complex enters the human body, the pH is around 7.4 and at that physiological pH, the dendrimer holds the drug tightly. Hence the release of drug can occur at a controlled rate into the bloodstream. Thus, our findings provide a microscopic picture of the encapsulation and controlled release of drugs in the case of dendrimer-based host-guest systems.

Delay Optimal Event Detection on Ad Hoc Wireless Sensor Networks

We consider a small extent sensor network for event detection, in which nodes periodically take samples and then contend over a random access network to transmit their measurement packets to the fusion center. We consider two procedures at the fusion center for processing the measurements. The Bayesian setting, is assumed, that is, the fusion center has a prior distribution on the change time. In the first procedure, the decision algorithm at the fusion center is network-oblivious and makes a decision only when a complete vector of measurements taken at a sampling instant is available. In the second procedure, the decision algorithm at the fusion center is network-aware and processes measurements as they arrive, but in a time-causal order. In this case, the decision statistic depends on the network delays, whereas in the network-oblivious case, the decision statistic does not. This yields a Bayesian change-detection problem with a trade-off between the random network delay and the decision delay that is, a higher sampling rate reduces the decision delay but increases the random access delay. Under periodic sampling, in the network-oblivious case, the structure of the optimal stopping rule is the same as that without the network, and the optimal change detection delay decouples into the network delay and the optimal decision delay without the network. In the network-aware case, the optimal stopping problem is analyzed as a partially observable Markov decision process, in which the states of the queues and delays in the network need to be maintained. A sufficient decision statistic is the network state and the posterior probability of change having occurred, given the measurements received and the state of the network. The optimal regimes are studied using simulation.

Fluoranthene based fluorescent chemosensors for detection of explosive nitroaromatics

A novel fluoranthene based fluorescent chemosensor for the detection of picric acid (PA) at the parts per billion (ppb) level was evaluated. Static fluorescence quenching was the dominant process by intercalative pi-pi interaction between fluoranthene (S-1) and nitroaromatics.

Incremental Cycle Detection, Topological Ordering, and Strong Component Maintenance

We present two online algorithms for maintaining a topological order of a directed n-vertex acyclic graph as arcs are added, and detecting a cycle when one is created. Our first algorithm handles m arc additions in O(m(3/2)) time. For sparse graphs (m/n = O(1)), this bound improves the best previous bound by a logarithmic factor, and is tight to within a constant factor among algorithms satisfying a natural locality property. Our second algorithm handles an arbitrary sequence of arc additions in O(n(5/2)) time. For sufficiently dense graphs, this bound improves the best previous bound by a polynomial factor. Our bound may be far from tight: we show that the algorithm can take Omega(n(2)2 root(2lgn)) time by relating its performance to a generalization of the k-levels problem of combinatorial geometry. A completely different algorithm running in Theta (n(2) log n) time was given recently by Bender, Fineman, and Gilbert. We extend both of our algorithms to the maintenance of strong components, without affecting the asymptotic time bounds.

Vehicle Detection Tool - VDtect

The report talks about the implementation of Vehicle Detection tool using opensource software - WxPython. The main functionality of this tool includes collection of data, plotting of magnetometer data and the count of the vehicles detected. The report list about how installation process and various functionality of the tool.

Ultrasonic Guided Wave Characterization and Damage Detection in Foam-core Sandwich Panel using PWAS and LDV

Lamb wave type guided wave propagation in foam core sandwich structures and detectability of damages using spectral analysis method are reported in this paper. An experimental study supported by theoretical evaluation of the guided wave characteristics is presented here that shows the applicability of Lamb wave type guided ultrasonic wave for detection of damage in foam core sandwich structures. Sandwich beam specimens were fabricated with 10 mm thick foam core and 0.3 mm thick aluminum face sheets. Thin piezoelectric patch actuators and sensors are used to excite and sense guided wave. Group velocity dispersion curves and frequency response of sensed signal are obtained experimentally. The nature of damping present in the sandwich panel is monitored by measuring the sensor signal amplitude at various different distances measured from the center of the linear phased array. Delaminations of increasing width are created and detected experimentally by pitch-catch interrogation with guided waves and wavelet transform of the sensed signal. Signal amplitudes are analyzed for various different sizes of damages to differentiate the damage size/severity. A sandwich panel is also fabricated with a planer dimension of 600 mm x 400 mm. Release film delamination is introduced during fabrication. Non-contact Laser Doppler Vibrometer (LDV) is used to scan the panel while exciting with a surface bonded piezoelectric actuator. Presence of damage is confirmed by the reflected wave fringe pattern obtained from the LDV scan. With this approach it is possible to locate and monitor the damages by tracking the wave packets scattered from the damages.

Guided Wave based Damage Detection in a Composite T-joint using 3D Scanning Laser Doppler Vibrometer

Composite T-joints are commonly used in modern composite airframe, pressure vessels and piping structures, mainly to increase the bending strength of the joint and prevents buckling of plates and shells, and in multi-cell thin-walled structures. Here we report a detailed study on the propagation of guided ultrasonic wave modes in a composite T-joint and their interactions with delamination in the co-cured co-bonded flange. A well designed guiding path is employed wherein the waves undergo a two step mode conversion process, one is due to the web and joint filler on the back face of the flange and the other is due to the delamination edges close to underneath the accessible surface of the flange. A 3D Laser Doppler Vibrometer is used to obtain the three components of surface displacements/velocities of the accessible face of the flange of the T-joint. The waves are launched by a piezo ceramic wafer bonded on to the back surface of the flange. What is novel in the proposed method is that the location of any change in material/geometric properties can be traced by computing a frequency domain power flow along a scan line. The scan line can be chosen over a grid either during scan or during post-processing of the scan data off-line. The proposed technique eliminates the necessity of baseline data and disassembly of structure for structural interrogation.

Electrochemical Detection of Bisphenol A Using Graphene-Modified Glassy Carbon Electrode

Graphene's nano-dimensional nature and excellent electron transfer properties underlie its electrocatalytic behavior towards certain substances. In this light, we have used graphene in the electrochemical detection of bisphenol A. Graphene sheets were produced via soft chemistry route involving graphite oxidation and chemical reduction. X-ray diffraction, Fourier transform infra-red (FT-IR) and Raman spectroscopy were used for the characterization of the as-synthesized graphene. Graphene exhibited amorphous structure in comparison with pristine graphite from XRD spectra. FTIR showed that graphene exhibits OH and COOH groups due to incomplete reduction. Raman spectroscopy revealed that multi-layered graphene was produced due to low intensity of the 2D-peak. Glassy carbon electrode was modified with graphene by a simple drop and dry method. Cyclic voltammetry was used to study the electrochemical properties of the prepared graphene-modified glassy carbon electrode using potassium ferricyanide as a redox probe. The prepared graphene- modified glassy carbon electrode exhibited more facile electron kinetics and enhanced current of about 75% when compared to the unmodified glassy carbon electrode. The modified electrode was used for the detection of bisphenol A. Under the optimum conditions, the oxidation peak current of bisphenol A varied linearly with concentration over a wide range of 5 x 10(-8) mol L-1 to 1 x 10(-6) mol L-1 and the detection limit of this method was as low as 4.689 x 10(-8) M. This method was also employed to determine bisphenol A in a real sample

Ultrasound Assisted Optical Tomography: Estimation of phase Shift experienced by photon on transit through US insonified region for detection of breast tumor

A Monte Carlo model of ultrasound modulation of multiply scattered coherent light in a highly scattering media has been carried out for estimating the phase shift experienced by a photon beam on its transit through US insonified region. The phase shift is related to the tissue stiffness, thereby opening an avenue for possible breast tumor detection. When the scattering centers in the tissue medium is exposed to a deterministic forcing with the help of a focused ultrasound (US) beam, due to the fact that US-induced oscillation is almost along particular direction, the direction defined by the transducer axis, the scattering events increase, thereby increasing the phase shift experienced by light that traverses through the medium. The phase shift is found to increase with increase in anisotropy g of the medium. However, as the size of the focused region which is the region of interest (ROI) increases, a large number of scattering events take place within the ROI, the ensemble average of the phase shift (Delta phi) becomes very close to zero. The phase of the individual photon is randomly distributed over 2 pi when the scattered photon path crosses a large number of ultrasound wavelengths in the focused region. This is true at high ultrasound frequency (1 MHz) when mean free path length of photon l(s) is comparable to wavelength of US beam. However, at much lower US frequencies (100 Hz), the wavelength of sound is orders of magnitude larger than l(s), and with a high value of g (g 0.9), there is a distinct measurable phase difference for the photon that traverses through the insonified region. Experiments are carried out for validation of simulation results.

Guided wave based detection of damage in honeycomb core sandwich structures

We report on the Lamb wave type guided wave propagation in honeycomb core sandwich structures. An experimental study supported by theoretical evaluation of the guided wave characteristics is presented that proves the potential of Lamb wave type guided wave for detection of damage in sandwich structures. A sandwich panel is fabricated with planar dimension of 600 mm x 600 mm, having a core thickness of 7 mm, cell size of 5 mm and 0.1 mm thick aluminum face sheets. Thin piezoelectric patch actuators and sensors are used to excite and sense a frequency band limited guided wave with a central frequency. A linear phased array of piezoelectric patch actuators is used to achieve higher signal strength and directivity. Group velocity dispersion curves and corresponding frequency response of sensed signal are obtained experimentally. Linearity between the excitation signal amplitude and the corresponding sensed signal amplitude is found for certain range of parameters. The nature of damping present in the sandwich panel is monitored by measuring the sensor signal amplitude at various different distances measured from the center of the linear phased array. Indentation and low velocity impact induced damages of increasing diameter covering several honeycomb cells are created. Crushing of honeycomb core with rupture of face sheet is observed while introducing the damage. The damages are then detected experimentally by pitch-catch interrogation with guided waves and wavelet transform of the sensed signal. Signal amplitudes are analyzed for various different sizes of damages to differentiate the damage size/severity. Monotonic changes in the sensor signal amplitude due to increase in the damage size has been established successfully. With this approach it is possible to locate and monitor the damages with the help of phased array and by tracking the wave packets scattered from the damages. (C) 2012 Elsevier Ltd. All rights reserved.

Selective colorimetric detection of nanomolar Cr (VI) in aqueous solutions using unmodified silver nanoparticles

In this study we present a colorimetric detection method for Cr (VI) in aqueous solution based on as synthesized silver nanoparticles (Ag NPs) without surface functionalization. The method principle involves reduction of Cr (VI) to Cr (III) by excess reductant present in as synthesized Ag NP dispersion, and subsequent aggregation of Ag NPs by Cr (III) leading to red-shift of the surface plasmon resonance (SPR) peak. The UV-vis absorption spectra. Zeta potentials, dynamic light scattering measurements, and scanning electron microscopy (SEM) confirmed the aggregation of the Ag NPs. Under the optimized conditions, a good linear relationship (correlation coefficient r=0.981) was obtained between the ratio of the absorbance at 550 nm to that at 390 nm (A(550/390)) and the concentration of Cr (VI) over the range of 10(-3)-10(-9) M 50 mg/L to 50 ng/L]. The reported probe has a limit of detection down to 1 nM, which, to the best of our knowledge, is the lowest ever reported for the colorimetric detection of Cr (VI). Furthermore, a remarkable feature of this method is that it involves a simple technique exhibiting high selectivity to Cr (VI) over other tested heavy metal ions. (C) 2012 Elsevier BM. All rights reserved.

Acidic pH induced STM1485 gene is essential for intracellular replication of Salmonella

During the course of infection, Salmonella has to face several potentially lethal environmental conditions, one such being acidic pH. The ability to sense and respond to the acidic pH is crucial for the survival and replication of Salmonella. The physiological role of one gene (STM1485) involved in this response, which is upregulated inside the host cells (by 90- to 113-fold) is functionally characterized in Salmonella pathogenesis. In vitro, the DSTM1485 neither exhibited any growth defect at pH 4.5 nor any difference in the acid tolerance response. The DSTM1485 was compromised in its capacity to proliferate inside the host cells and complementation with STM1485 gene restored its virulence. We further demonstrate that the surface translocation of Salmonella pathogenicity island-2 (SPI-2) encoded translocon proteins, SseB and SseD were reduced in the DSTM1485. The increase in co-localization of this mutant with lysosomes was also observed. In addition, the DSTM1485 displayed significantly reduced competitive indices (CI) in spleen, liver and mesenteric lymph nodes in murine typhoid model when infected by intra-gastric route. Based on these results, we conclude that the acidic pH induced STM1485 gene is essential for intracellular replication of Salmonella.

Cascaded walks in protein sequence space: use of artificial sequences in remote homology detection between natural proteins

Over the past two decades, many ingenious efforts have been made in protein remote homology detection. Because homologous proteins often diversify extensively in sequence, it is challenging to demonstrate such relatedness through entirely sequence-driven searches. Here, we describe a computational method for the generation of `protein-like' sequences that serves to bridge gaps in protein sequence space. Sequence profile information, as embodied in a position-specific scoring matrix of multiply aligned sequences of bona fide family members, serves as the starting point in this algorithm. The observed amino acid propensity and the selection of a random number dictate the selection of a residue for each position in the sequence. In a systematic manner, and by applying a `roulette-wheel' selection approach at each position, we generate parent family-like sequences and thus facilitate an enlargement of sequence space around the family. When generated for a large number of families, we demonstrate that they expand the utility of natural intermediately related sequences in linking distant proteins. In 91% of the assessed examples, inclusion of designed sequences improved fold coverage by 5-10% over searches made in their absence. Furthermore, with several examples from proteins adopting folds such as TIM, globin, lipocalin and others, we demonstrate that the success of including designed sequences in a database positively sensitized methods such as PSI-BLAST and Cascade PSI-BLAST and is a promising opportunity for enormously improved remote homology recognition using sequence information alone.