Gene Transfection in High Serum Levels: Case Studies with New Cholesterol Based Cationic Gemini Lipids

Background: Six new cationic gemini lipids based on cholesterol possessing different positional combinations of hydroxyethyl (-CH2CH2OH) and oligo-oxyethylene -(CH2CH2O)(n)- moieties were synthesized. For comparison the corresponding monomeric lipid was also prepared. Each new cationic lipid was found to form stable, clear suspensions in aqueous media. Methodology/Principal Findings: To understand the nature of the individual lipid aggregates, we have studied the aggregation properties using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements and X-ray diffraction (XRD). We studied the lipid/DNA complex (lipoplex) formation and the release of the DNA from such lipoplexes using ethidium bromide. These gemini lipids in presence of a helper lipid, 1, 2-dioleoyl phophatidyl ethanol amine (DOPE) showed significant enhancements in the gene transfection compared to several commercially available transfection agents. Cholesterol based gemini having -CH2-CH2-OH groups at the head and one oxyethylene spacer was found to be the most effective lipid, which showed transfection activity even in presence of high serum levels (50%) greater than Effectene, one of the potent commercially available transfecting agents. Most of these geminis protected plasmid DNA remarkably against DNase I in serum, although the degree of stability was found to vary with their structural features. Conclusions/Significance: -OH groups present on the cationic headgroups in combination with oxyethylene linkers on cholesterol based geminis, gave an optimized combination of new genera of gemini lipids possessing high transfection efficiency even in presence of very high percentage of serum. This property makes them preferential transfection reagents for possible in vivo studies.

New insights into designing metallacarborane based room temperature hydrogen storage media

Metallacarboranes are promising towards realizing room temperature hydrogen storage media because of the presence of both transition metal and carbon atoms. In metallacarborane clusters, the transition metal adsorbs hydrogen molecules and carbon can link these clusters to form metal organic framework, which can serve as a complete storage medium. Using first principles density functional calculations, we chalk out the underlying principles of designing an efficient metallacarborane based hydrogen storage media. The storage capacity of hydrogen depends upon the number of available transition metal d-orbitals, number of carbons, and dopant atoms in the cluster. These factors control the amount of charge transfer from metal to the cluster, thereby affecting the number of adsorbed hydrogen molecules. This correlation between the charge transfer and storage capacity is general in nature, and can be applied to designing efficient hydrogen storage systems. Following this strategy, a search for the best metallacarborane was carried out in which Sc based monocarborane was found to be the most promising H-2 sorbent material with a 9 wt.% of reversible storage at ambient pressure and temperature. (C) 2013 AIP Publishing LLC.

On the nature of meandering of the springtime western boundary current in the Bay of Bengal

We present evidence that the springtime western boundary current (WBC) in the Bay of Bengal is a continuous northward-flowing current from about 12 degrees N to 17 degrees N, which then separates from the coast at around 18 degrees N. We first revisit a hydrographic data set collected in 1987 from a potential vorticity perspective, and then analyze absolute dynamic height maps from satellite altimeters during the period 2000-2010. The altimetric maps suggest that the mean configuration of the WBC is that of an intense current with two anticyclonic eddies on the offshore side, which are part of the basin-wide anticyclonic circulation. The WBC consistently separates from the coast at around 18 degrees N in all years between 2000 and 2010. The path of the eastward-flowing mean stream after separation appears to be consistent with isolines of f/H and with Ertel's potential vorticity, based on an analysis of the hydrographic data from 1987.

EESM-Based Link Adaptation in Point-to-Point and Multi-Cell OFDM Systems: Modeling and Analysis

In contemporary wideband orthogonal frequency division multiplexing (OFDM) systems, such as Long Term Evolution (LTE) and WiMAX, different subcarriers over which a codeword is transmitted may experience different signal-to-noise-ratios (SNRs). Thus, adaptive modulation and coding (AMC) in these systems is driven by a vector of subcarrier SNRs experienced by the codeword, and is more involved. Exponential effective SNR mapping (EESM) simplifies the problem by mapping this vector into a single equivalent fiat-fading SNR. Analysis of AMC using EESM is challenging owing to its non-linear nature and its dependence on the modulation and coding scheme. We first propose a novel statistical model for the EESM, which is based on the Beta distribution. It is motivated by the central limit approximation for random variables with a finite support. It is simpler and as accurate as the more involved ad hoc models proposed earlier. Using it, we develop novel expressions for the throughput of a point-to-point OFDM link with multi-antenna diversity that uses EESM for AMC. We then analyze a general, multi-cell OFDM deployment with co-channel interference for various frequency-domain schedulers. Extensive results based on LTE and WiMAX are presented to verify the model and analysis, and gain new insights.

A New Voltage Stability Index based on the Tangent Vector of the Power Flow Jacobian

This paper presents a new voltage stability index based on the tangent vector of the power flow jacobian. This index is capable of providing the relative vulnerability information of the system buses from the point of view of voltage collapse. In an effort to compare this index with a similar index, the popular voltage stability index L is studied and it is shown through system studies that the L index is not a very consistent indicator of the voltage collapse point of the system but is only a reasonable indicator of the vulnerability of the system buses to voltage collapse. We also show that the new index can be used in the voltage stability analysis of radial systems which is not possible with the L index. This is a significant result of this investigation since there is a lot of contemporary interest in distributed generation and microgrids which are by and large radial in nature. Simulation results considering several test systems are provided to validate the results and the computational needs of the proposed scheme is assessed in comparison with other schemes

Tripodal Bile Acid Architectures Based on a Triarylphosphine Oxide Core Obtained by Copper-Catalysed 1,3]-Dipolar Cycloaddition: Synthesis and Preliminary Aggregation Studies

We report the synthesis and aggregation behaviour of new water-soluble, bile acid derived tripodal architectures based on a core derived from triphenylphosphine oxide. We employed the well-established copper-catalysed 1,3]-dipolar cycloaddition (CuAAC) for the construction of these tripodal molecules. The aggregation behaviour of these molecules in aqueous media was studied by different analytical methods such as dye solubilisation, dynamic light scattering, NMR and AFM. These molecular architectures also offer an additional advantage in aiding understanding of the influence of the nature of the bile acid backbone and of the configuration at the steroid C-3 position in these architectures; to the best of our knowledge this has not been reported in the literature. The unique gelation properties of the -derivatives were explained through molecular modelling studies and the mechanical behaviour of these gels was studied by rheology experiments.

Model-Resolution-Based Basis Pursuit Deconvolution Improves Diffuse Optical Tomographic Imaging

The image reconstruction problem encountered in diffuse optical tomographic imaging is ill-posed in nature, necessitating the usage of regularization to result in stable solutions. This regularization also results in loss of resolution in the reconstructed images. A frame work, that is attributed by model-resolution, to improve the reconstructed image characteristics using the basis pursuit deconvolution method is proposed here. The proposed method performs this deconvolution as an additional step in the image reconstruction scheme. It is shown, both in numerical and experimental gelatin phantom cases, that the proposed method yields better recovery of the target shapes compared to traditional method, without the loss of quantitativeness of the results.

Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors

The nucleoid-associated protein HU plays an important role in maintenance of chromosomal architecture and in global regulation of DNA transactions in bacteria. Although HU is essential for growth in Mycobacterium tuberculosis (Mtb), there have been no reported attempts to perturb HU function with small molecules. Here we report the crystal structure of the N-terminal domain of HU from Mtb. We identify a core region within the HU-DNA interface that can be targeted using stilbene derivatives. These small molecules specifically inhibit HU-DNA binding, disrupt nucleoid architecture and reduce Mtb growth. The stilbene inhibitors induce gene expression changes in Mtb that resemble those induced by HU deficiency. Our results indicate that HU is a potential target for the development of therapies against tuberculosis.

Solving Dynamic Constraint Single Objective Functions using a Nature Inspired Technique

We present in this paper a new algorithm based on Particle Swarm Optimization (PSO) for solving Dynamic Single Objective Constrained Optimization (DCOP) problems. We have modified several different parameters of the original particle swarm optimization algorithm by introducing new types of particles for local search and to detect changes in the search space. The algorithm is tested with a known benchmark set and compare with the results with other contemporary works. We demonstrate the convergence properties by using convergence graphs and also the illustrate the changes in the current benchmark problems for more realistic correspondence to practical real world problems.

Estimates of site response based on spectral ratio between horizontal and vertical components of ambient vibrations in the source zone of 2001 Bhuj earthquake

We investigated the site response characteristics of Kachchh rift basin over the meizoseismal area of the 2001, Mw 7.6, Bhuj (NW India) earthquake using the spectral ratio of the horizontal and vertical components of ambient vibrations. Using the available knowledge on the regional geology of Kachchh and well documented ground responses from the earthquake, we evaluated the H/V curves pattern across sediment filled valleys and uplifted areas generally characterized by weathered sandstones. Although our HIV curves showed a largely fuzzy nature, we found that the hierarchical clustering method was useful for comparing large numbers of response curves and identifying the areas with similar responses. Broad and plateau shaped peaks of a cluster of curves within the valley region suggests the possibility of basin effects within valley. Fundamental resonance frequencies (f(0)) are found in the narrow range of 0.1-2.3 Hz and their spatial distribution demarcated the uplifted regions from the valleys. In contrary, low HIV peak amplitudes (A(0) = 2-4) were observed on the uplifted areas and varying values (2-9) were found within valleys. Compared to the amplification factors, the liquefaction indices (kg) were able to effectively indicate the areas which experienced severe liquefaction. The amplification ranges obtained in the current study were found to be comparable to those obtained from earthquake data for a limited number of seismic stations located on uplifted areas; however the values on the valley region may not reflect their true amplification potential due to basin effects. Our study highlights the practical usefulness as well as limitations of the HIV method to study complex geological settings as Kachchh. (C) 2014 Elsevier Ltd. All rights reserved.

Emergency Handling in MICS based Body Area Network

Body Area Network, a new wireless networking paradigm, promises to revolutionize the healthcare applications. A number of tiny sensor nodes are strategically placed in and around the human body to obtain physiological information. The sensor nodes are connected to a coordinator or a data collector to form a Body Area Network. The tiny devices may sense physiological parameters of emergency in nature (e.g. abnormality in heart bit rate, increase of glucose level above the threshold etc.) that needs immediate attention of a physician. Due to ultra low power requirement of wireless body area network, most of the time, the coordinator and devices are expected to be in the dormant mode, categorically when network is not operational. This leads to an open question, how to handle and meet the QoS requirement of emergency data when network is not operational? Emergency handling becomes more challenging at the MAC layer, if the channel access related information is unknown to the device with emergency message. The aforementioned scenarios are very likely scenarios in a MICS (Medical Implant Communication Service, 402-405 MHz) based healthcare systems. This paper proposes a mechanism for timely and reliable transfer of emergency data in a MICS based Body Area Network. We validate our protocol design with simulation in a C++ framework. Our simulation results show that more than 99 p ercentage of the time emergency messages are reached at the coordinator with a delay of 400ms.

Graphene based multifunctional flame sensor

Recently, graphene has attracted much attention due to its unique electrical and thermal properties along with its high surface area, and hence presents an ideal sensing material. We report a novel configuration of a graphene based flame sensor by exploiting the response of few layer graphene to a flame along two different directions, where flame detection results from a difference in heat transfer mechanisms. A complete sensor module was developed with a signal conditioning circuit that compensates for any drift in the baseline of the sensor, along with a flame detection algorithm implemented in a microcontroller to detect the flame. A pre-defined threshold for either of the sensors is tunable, which can be varied based on the nature of the flame, hence presenting a system that can be used for detection of any kind of flame. This finding also presents a scalable method that opens avenues to modify complicated sensing schemes.

High T-g fluoranthene-based electron transport materials for organic light-emitting diodes

In this study, fluoranthene-based derivatives with a high thermal stability were synthesized for applications in organic electroluminescent devices. The two derivatives synthesized in this study, bis(4-(7,9,10-triphenylfluoranthen-8-yl)phenyl)sulfane (TPFDPS) and 2,8-bis(7,9,10-triphenylfluoranthen-8-yl)dibenzob,d]thiophene (TPFDBT), were characterized by cyclic voltammetry, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). TPFDPS exhibits a high T-g of 210 degrees C while TPFDBT is crystalline in nature. Both the derivatives are thermally stable up to 500 degrees C. The charge transport studies reveal predominant electron transport properties. Subsequently, we fabricated blue OLEDs with 2-tert-butyl-9,10-bis-(beta-naphthyl)-anthracene (TBADN) as the emitting layer to demonstrate the applications of these molecules as an electron transporting layer.

A TDMA-based Energy Aware MAC (TEA-MAC) Protocol for Reliable Multicast in WSNs

Multicast in wireless sensor networks (WSNs) is an efficient way to spread the same data to multiple sensor nodes. It becomes more effective due to the broadcast nature of wireless link, where a message transmitted from one source is inherently received by all one-hop receivers, and therefore, there is no need to transmit the message one by one. Reliable multicast in WSNs is desirable for critical tasks like code updation and query based data collection. The erroneous nature of wireless medium coupled with limited resource of sensor nodes, makes the design of reliable multicast protocol a challenging task. In this work, we propose a time division multiple access (TDMA) based energy aware media access and control (TEA-MAC) protocol for reliable multicast in WSNs. The TDMA eliminates collisions, overhearing and idle listening, which are the main sources of reliability degradation and energy consumption. Furthermore, the proposed protocol is parametric in the sense that it can be used to trade-off reliability with energy and delay as per the requirement of the underlying applications. The performance of TEA-MAC has been evaluated by simulating it using Castalia network simulator. Simulation results show that TEA-MAC is able to considerably improve the performance of multicast communication in WSNs.

Imidazolium based ionic liquid type surfactant improves activity and thermal stability of lipase of Rhizopus oryzae

Lipase and surfactant together form a potent pair in various biotransformation, industrial application and biotechnological studies. The present investigation deals with changes in the activity, stability and structure of lipase from Rhizopus oryzae NRRL 3562 in presence of long chain ionic liquid-type imidazolium surfactant. Both the activity and stability were found to be enhanced in presence of the surfactant at low concentration (1-125 mu M) followed by inhibition at high concentration. The activity increased by 80% and thermal deactivation temperature raised by 2.5 degrees C. Investigations by ultraviolet-visible spectroscopy and circular dichroism revealed structural changes leading to rise in beta-sheet content and lowering of a-helix at low surfactant concentrations. Deactivation at high concentration correlated with greater structural changes depicted by spectroscopic studies. Isothermal titration calorimetric studies showed the binding to be spontaneous in nature involving non-covalent interactions. High negative value of entropy signifies exposure of hydrophobic domains and increase in structural rigidity, which correlates with active site being more accessible and rigid in presence of the surfactant. Application of these surfactants hold greater potential in the field of lipase based biotransformations, enzyme structural modifications and studies. (C) 2015 Elsevier B.V. All rights reserved.