Comparative study of different nonconserving time integrators for wave propagation in hyperelastic waveguides

This paper addresses the formulation and numerical efficiency of various numerical models of different nonconserving time integrators for studying wave propagation in nonlinear hyperelastic waveguides. The study includes different nonlinear finite element formulations based on standard Galerkin finite element model, time domain spectral finite element model, Taylor-Galerkin finite element model, generalized Galerkin finite element model and frequency domain spectral finite element model. A comparative study on the computational efficiency of these different models is made using a hyperelastic rod model, and the optimal computational scheme is identified. The identified scheme is then used to study the propagation of transverse and longitudinal waves in a Timoshenko beam with Murnaghan material nonlinearity.

Mixed finite elements for electromagnetic analysis

The occurrence of spurious solutions is a well-known limitation of the standard nodal finite element method when applied to electromagnetic problems. The two commonly used remedies that are used to address this problem are (i) The addition of a penalty term with the penalty factor based on the local dielectric constant, and which reduces to a Helmholtz form on homogeneous domains (regularized formulation); (ii) A formulation based on a vector and a scalar potential. Both these strategies have some shortcomings. The penalty method does not completely get rid of the spurious modes, and both methods are incapable of predicting singular eigenvalues in non-convex domains. Some non-zero spurious eigenvalues are also predicted by these methods on non-convex domains. In this work, we develop mixed finite element formulations which predict the eigenfrequencies (including their multiplicities) accurately, even for nonconvex domains. The main feature of the proposed mixed finite element formulation is that no ad-hoc terms are added to the formulation as in the penalty formulation, and the improvement is achieved purely by an appropriate choice of finite element spaces for the different variables. We show that the formulation works even for inhomogeneous domains where `double noding' is used to enforce the appropriate continuity requirements at an interface. For two-dimensional problems, the shape of the domain can be arbitrary, while for the three-dimensional ones, with our current formulation, only regular domains (which can be nonconvex) can be modeled. Since eigenfrequencies are modeled accurately, these elements also yield accurate results for driven problems. (C) 2014 Elsevier Ltd. All rights reserved.

Efficacious Gene Silencing in Serum and Significant Apoptotic Activity Induction by Survivin Downregulation Mediated by New Cationic Gemini Tocopheryl Lipids

Nonviral gene delivery offers cationic liposomes as promising instruments for the delivery of double-stranded RNA (ds RNA) molecules for successful sequence-specific gene silencing (RNA interference). The efficient delivery of siRNA (small interfering RNA) to cells while avoiding unexpected side effects is an important prerequisite for the exploitation of the power of this excellent tool. We present here six new tocopherol based cationic gemini lipids, which induce substantial gene knockdown without any obvious cytotoxicity. All the efficient coliposomal formulations derived from each of these geminis and a helper lipid, dioleoylphosphatidylethanolamine (DOPE), were well characterized using physical methods such as atomic force microscopy (AFM) and dynamic light scattering (DLS). Zeta potential measurements were conducted to estimate the surface charge of these formulations. Flow cytometric analysis showed that the optimized coliposomal formulations could transfect anti-GFP siRNA efficiently in three different GFP expressing cell lines, viz., HEK 293T, HeLa, and Caco-2, significantly better than a potent commercial standard Lipofectamine 2000 (L2K) both in the absence and in the presence of serum (FBS). Notably, the knockdown activity of coliposomes of gemini lipids was not affected even in the presence of serum (10% and 50% FBS) while it dropped down for L2K significantly. Observations under a fluorescence microscope, RT-PCR, and Western blot analysis substantiated the flow cytometry results. The efficient cellular entry of labeled siRNA in GFP expressing cells as evidenced from confocal microscopy put forward these gemini lipids among the potent lipidic carriers for siRNA. The efficient transfection capabilities were also profiled in a more relevant fashion while performing siRNA transfections against survivin (an anti-apoptotic protein) which induced substantial apoptosis. Furthermore, the survivin downregulation improved the therapeutic efficacy levels of an anticancer drug, doxorubicin, significantly. In short, the new tocopherol based gemini lipids appear to be highly promising for achieving siRNA mediated gene knockdown in various cell lines.

A delocalizable cationic headgroup together with an oligo-oxyethylene spacer in gemini cationic lipids improves their biological activity as vectors of plasmid DNA

Lipoplex nano-aggregates constituted of plasmid DNA (pDNA) pEGFP-C3 and mixed cationic liposomes, consisting of several percentages of a gemini cationic lipid (GCL) of the 1,2-bis(hexadecyl imidazolium) oxyethylene series, referred to as (C(16)Im)(2)(C2O)(n), with oxyethylene spacers (n = 1, 2 or 3) between the imidazolium cationic groups and the DOPE zwitterionic helper lipid, have been characterized by various biophysical and biological approaches carried out at several GCL compositions (alpha), and either the mass or the effective charge ratio of the lipoplex. The electrochemical study by zeta-potential confirms that the three GCLs yield a 10% lower effective charge than the nominal one, while compacted pDNA yields only a 25% effective negative charge. The SAXS study reveals, irrespective of the spacer length (n) and effective charge ratio (rho(eff)), the presence of two lamellar structures, i.e., one (L-alpha,L-main) in the whole GCL composition and another (L-alpha,L-DOPE,L-rich) with higher periodicity values that coexists with the previous one at low GCL composition (alpha = 0.2). The cryo-TEM analysis shows two types of multilamellar structures consisting of cationic lipidic bilayers with pDNA sandwiched between them: a cluster-type (C-type) at low alpha = 0.2 and a fingerprint-type (FP-type) at alpha >= 0.5, both with similar interlamellar spacing (d) in agreement with the L-alpha,L-main structure determined by SAXS. Transfection efficacies (TEs) of each lipid mixture were determined in four different cell lines (HEK293T, HeLa, Caco-2 and A549) at several alpha and rho(eff) values in the absence and presence of serum (FBS). The optimized formulations (alpha = 0.2 and rho(eff) = 2.0) substantially transfect cells much better than a commercial transfection reagent, Lipofectamine 2000 and previously studied efficient lipoplexes containing other cationic head groups or spacers both in the absence and presence of serum. The activity of optimized formulations may be attributed to the combination of several factors, such as: (a) the fusogenic character of DOPE which results in higher fluidity of the lipoplexes at alpha = 0.2, (b) the coexistence of two lamellar structures at alpha = 0.2 that synergizes the TE of these lipid vectors, and mainly (c) the higher biocompatibility of the GCLs reported in this work due to the presence of two imidazolium cationic groups together with an oligo-oxyethylene spacer. The length of the spacer in the GCL seems to have less impact, although (C(16)Im)(2)(C2O)(n)/DOPEpDNA lipoplexes with n = 1 and 3 show higher gene transfection than n = 2. All the optimum formulations reported herein are all highly efficient with negligible levels of toxicity, and thus, may be considered as very promising gene vectors for in vivo applications.

alpha-Tocopherol derived lipid dimers as efficient gene transfection agents. Mechanistic insights into lipoplex internalization and therapeutic induction of apoptotic activity

In this report, we present cationic dimeric (gemini) lipids for significant plasmid DNA (pDNA) delivery to different cell lines without any marked toxicity in the presence of serum. Six gemini lipids based on alpha-tocopherol were synthesized, which differed in their spacer chain lengths. Each of these gemini lipids mixed with a helper lipid, 1,2-dioleoyl phosphatidyl ethanolamine (DOPE), was capable of forming stable aqueous suspensions. These co-liposomal systems were examined for their potential to transfect pEGFP-C3 plasmid DNA into nine cell lines of different origins. The transfection efficacies noticed in terms of EGFP expression levels using flow cytometry were well corroborated using independent fluorescence microscopy studies. Significant EGFP expression levels were reported using the gemini co-liposomes, which counted significantly better than one well known commercial formulation, Lipofectamine 2000 (L2 K). Transfection efficacies were also analyzed in terms of the degree of intracellular delivery of labeled plasmid DNA (pDNA) using confocal microscopy, which revealed an efficient internalization in the presence of serum. The cell viability assays performed using optimized formulations demonstrated no significant toxicity towards any of the cell lines used in the study. We also had a look at the lipoplex internalization pathway to profile the uptake characteristics. A caveolae/lipid raft route was attributed to their excellent gene transfection capabilities. The study was further advanced by using a therapeutic p53-EGFP-C3 plasmid and the apoptotic activity was observed using FACS and growth inhibition assay.

Co-liposomes of redox-active alkyl-ferrocene modified low MW branched PEI and DOPE for efficacious gene delivery in serum

Herein, we present six new lipopolymers based on low molecular weight, branched polyethylenimine (BPEI 800 Da) which are hydrophobically modified using ferrocene terminated alkyl tails of variable lengths. The effects of degree of grafting, spacer length and the redox state of ferrocene in the lipopolymers on the self assembly properties were investigated in detail by TEM, AFM, DLS and zeta potential measurements. The assemblies displayed an oxidation induced increase in the size of the aggregates. The co-liposomes comprising the lipopolymer and a helper lipid, 1,2-dioleoyl phosphatidyl ethanolamine (DOPE), showed excellent gene (pDNA) delivery capability in a serum containing environment in two cancer cell lines (HeLa and U251 cells). Optimized formulations showed remarkably higher transfection activity than BPEI (25 kDa) and were also significantly better than a commercial transfection reagent, Lipofectamine 2000 as evidenced from both the luciferase activity and GFP expression analysis. Oxidation of ferrocene in the lipopolymers led to drastically reduced levels of gene transfection which was substantiated by reduced cellular internalization of fluorescently labelled pDNA as detected using confocal microscopy and flow cytometry. Moreover, the transfection inactive oxidized lipopolyplexes could be turned transfection active by exposure to ascorbic acid (AA) in cell culture medium during transfection. Endocytosis inhibition experiments showed that gene expression mediated by reduced formulations involved both clathrin and caveolae mediated pathways while the oxidized formulations were routed via the caveolae. Cytotoxicity assays revealed no obvious toxicity for the lipopolyplexes in the range of optimized transfection levels in both the cell lines studied. Overall, we have exploited the redox activity of ferrocene in branched PEI-based efficient polymeric gene carriers whose differential transfection activities could be harnessed for spatial or temporal cellular transfections.

Hybrid Elements for Modelling Squeeze Film Effects Coupled with Structural Interactions in Vibratory MEMS Devices

We present a hybrid finite element based methodology to solve the coupled fluid structure problem of squeeze film effects in vibratory MEMS devices, such as gyroscopes, RF switches, and 2D resonators. The aforementioned devices often have a thin plate like structure vibrating normally to a fixed substrate, and are generally not perfectly vacuum packed. This results in a thin air film being trapped between the vibrating plate and the fixed substrate which behaves like a squeeze film offering both stiffness and damping. For accurate modelling of such devices the squeeze film effects must be incorporated. Extensive literature is available on squeeze film modelling, however only a few studies address the coupled fluid elasticity problem. The majority of the studies that account for the plate elasticity coupled with the fluid equation, either use approximate mode shapes for the plate or use iterative solution strategies. In an earlier work we presented a single step coupled methodology using only one type of displacement based element to solve the coupled problem. The displacement based finite element models suffer from locking issues when it comes to modelling very thin structures with the lateral dimensions much larger than the plate thickness as is typical in MEMS devices with squeeze film effects. In this work we present another coupled formulation where we have used hybrid elements to model the structural domain. The numerical results show a huge improvement in convergence and accuracy with coarse hybrid mesh as compared to displacement based formulations. We further compare our numerical results with experimental data from literature and find them to be in good accordance.

Pluronic copolymer encapsulated SCR7 as a potential anticancer agent

Nonhomologous end joining (NHEJ) of DNA double strand breaks (DSBs) inside cells can be selectively inhibited by 5,6-bis-(benzylideneamino)-2-mercaptopyrimidin-4-ol (SCR7) which possesses anticancer properties. The hydrophobicity of SCR7 decreases its bioavailability which is a major setback in the utilization of this compound as a therapeutic agent. In order to circumvent the drawback of SCR7, we prepared a polymer encapsulated form of SCR7. The physical interaction of SCR7 and Pluronic (R) copolymer is evident from different analytical techniques. The in vitro cytotoxicity of the drug formulations is established using the MTT assay.

Optimal power allocation for protective jamming in wireless networks: A flow based model

We address the problem of passive eavesdroppers in multi-hop wireless networks using the technique of friendly jamming. The network is assumed to employ Decode and Forward (DF) relaying. Assuming the availability of perfect channel state information (CSI) of legitimate nodes and eavesdroppers, we consider a scheduling and power allocation (PA) problem for a multiple-source multiple-sink scenario so that eavesdroppers are jammed, and source-destination throughput targets are met while minimizing the overall transmitted power. We propose activation sets (AS-es) for scheduling, and formulate an optimization problem for PA. Several methods for finding AS-es are discussed and compared. We present an approximate linear program for the original nonlinear, non-convex PA optimization problem, and argue that under certain conditions, both the formulations produce identical results. In the absence of eavesdroppers' CSI, we utilize the notion of Vulnerability Region (VR), and formulate an optimization problem with the objective of minimizing the VR. Our results show that the proposed solution can achieve power-efficient operation while defeating eavesdroppers and achieving desired source-destination throughputs simultaneously. (C) 2015 Elsevier B.V. All rights reserved.

Suppression of protein aggregation by gold nanoparticles: a new way to store and transport proteins

Suppression of the aggregation of proteins has tremendous implications in biology and medicine. In the pharmaceuticals industry, aggregation of therapeutically important proteins and peptides while stored, reduces the efficacy and promptness of action leading to, in many instances, intoxication of the patient by the aggregate. Here we report the effect of gold nanoparticles (Au-NPs) in preventing the thermal and chemical aggregation of two unrelated proteins of different size, alcohol dehydrogenase (ADH, 84 kDa) and insulin (6 kDa), respectively, in physiological pH. Our principal observation is that there is a significant reduction (up to 95%) in the extent of aggregation of ADH and insulin in the presence of gold nanoparticles (Au-NPs). Aggregation of these proteins at micromolar concentration is prevented using nanomolar or less amounts of gold nanoparticles which is remarkable since chaperones which prevent such aggregation in vivo are required in micromolar quantity. The prevention of aggregation of these two different proteins under two different denaturing environments has established the role of Au-NPs as a protein aggregation prevention agent. The extent of prevention increases rapidly with the increase in the size of the gold nanoparticles. Protein molecules get physisorbed on the gold nanoparticle surface and thus become inaccessible by the denaturing agent in solution. This adsorption of proteins on AuNPs has been established by a variety of techniques and assays.

Multicomponent Adducts of Pyridoxine: An Evaluation of the Formation of Eutectics and Molecular Salts

Cocrystallization of pyridoxine (vitamin B6) with several biologically important molecules was undertaken with the intent of successfully designing various hydrogen bonded adducts such as salts, cocrystals, and eutectics. Pyridoxine formed eutectics with isoniazid (an antitubercular drug) and nicotinic acid (vitamin B3) and molecular salts with para-aminobenzoic acid (a bioactive) and saccharin (an artificial sweetener), respectively, in accordance to our design strategy. A salt cocrystal, a precisely conjugate acid-base cocrystal, was obtained for the pyridoxine-para-nitrobenzoic acid combination. The role of supramolecular affinity of hydrogen bonding functional groups and Delta pK(a) differences leading to the formation of above diverse adducts was discussed. This study underpins the need for full-fledged supramolecular compatibility studies of multivitamin/drug combinations toward the development of optimal and/or synergistic combination formulations.

In-plane elastic responses of circular cell honeycombs and bundled circular tubes in a diamond array structure

Assemblages of circular tubes and circular honeycombs in close packed arrangement are presently both competing and complementing regular honeycomb structures (HCS). The intrinsic isotropy of bundled tubes/rings in hexagonal arrays restricts their use to applications with isotopic need. With the aim of extending the utility of tubes/rings assemblages to anisotropic needs, this paper explores the prospects of bundled tubes and circular honeycombs in a general diamond array structure (DAS) to cater these needs. To this end, effective transverse Young's moduli and Poisson's ratio for thick/thin DAS are obtained theoretically. Analysis frameworks including thin ring theory (TRT), curved beam theory (CBT) and elasticity formulations are tested and corroborated by FEA employing contact elements. Results indicate that TRT and CBT are reasonable for thin tubes and honeycombs. Nevertheless, TRT yields compact formulae to study the anisotropy ratio, moduli spectrum and sensitivity of the assemblage as a function of thicknesses and array structure. These formulae supplement designers as a guide to tailor the structures. On the other hand, elasticity formulation can estimate over a larger range including very thick tubes/rings. In addition, this formulation offers to estimate refined transverse strengths of assemblages. (C) 2015 Elsevier Ltd. All rights reserved.

Phytomedicinal importance of Saraca asoca (Ashoka): an exciting past, an emerging present and a promising future

Since the dawn of civilization, natural resources have remained the mainstay of various remedial approaches of humans vis-a-vis a large number of illnesses. Saraca asoca (Roxb.) de Wilde (Saraca indica L.) belonging to the family Caesalpiniaceae has been regarded as a universal panacea in old Indian Ayurvedic texts and has especially been used to manage gynaecological complications and infections besides treating haemmorhagic dysentery, uterine pain, bacterial infections, skin problems, tumours, worm infestations, cardiac and circulatory problems. Almost all parts of the plant are considered pharmacologically valuable. Extensive folkloric practices and ethnobotanical applications of this plant have even lead to the availability of several commercial S. asoca formulations recommended for different indications though adulteration of these remains a pressing concern. Though a wealth of knowledge on this plant is available in both the classical and modern literature, extensive research on its phytomedicinal worth using state-of-the-art tools and methodologies is lacking. Recent reports on bioprospecting of S. asoca endophytic fungi for industrial bioproducts and useful pharmacologically relevant metabolites provide a silver lining to uncover single molecular bio-effectors from its endophytes. Here, we describe socio-ethnobotanical usage, present the current pharmacological status and discuss potential bottlenecks in harnessing the proclaimed phytomedicinal worth of this prescribed Ayurvedic medicinal plant. Finally, we also look into the possible future of the drug discovery and pharmaceutical R&D efforts directed at exploring its pharma legacy.

Evaluation of the Index-Flood Approach Related Regional Frequency Analysis Procedures

Index-flood related regional frequency analysis (RFA) procedures are in use by hydrologists to estimate design quantiles of hydrological extreme events at data sparse/ungauged locations in river basins. There is a dearth of attempts to establish which among those procedures is better for RFA in the L-moment framework. This paper evaluates the performance of the conventional index flood (CIF), the logarithmic index flood (LIF), and two variants of the population index flood (PIF) procedures in estimating flood quantiles for ungauged locations by Monte Carlo simulation experiments and a case study on watersheds in Indiana in the U.S. To evaluate the PIF procedure, L-moment formulations are developed for implementing the procedure in situations where the regional frequency distribution (RFD) is the generalized logistic (GLO), generalized Pareto (GPA), generalized normal (GNO) or Pearson type III (PE3), as those formulations are unavailable. Results indicate that one of the variants of the PIF procedure, which utilizes the regional information on the first two L-moments is more effective than the CIF and LIF procedures. The improvement in quantile estimation using the variant of PIF procedure as compared with the CIF procedure is significant when the RFD is a generalized extreme value, GLO, GNO, or PE3, and marginal when it is GPA. (C) 2015 American Society of Civil Engineers.

Hydrogen energy future with formic acid: a renewable chemical hydrogen storage system

Formic acid, the simplest carboxylic acid, is found in nature or can be easily synthesized in the laboratory (major by-product of some second generation biorefinery processes); it is also an important chemical due to its myriad applications in pharmaceuticals and industry. In recent years, formic acid has been used as an important fuel either without reformation (in direct formic acid fuel cells, DFAFCs) or with reformation (as a potential chemical hydrogen storage material). Owing to the better efficiency of DFAFCs compared to several other PEMFCs and reversible hydrogen storage systems, formic acid could serve as one of the better fuels for portable devices, vehicles and other energy-related applications in the future. This perspective is focused on recent developments in the use of formic acid as a reversible source for hydrogen storage. Recent developments in this direction will likely give access to a variety of low-cost and highly efficient rechargeable hydrogen fuel cells within the next few years by the use of suitable homogeneous metal complex/heterogeneous metal nanoparticle-based catalysts under ambient reaction conditions. The production of formic acid from atmospheric CO2 (a greenhouse gas) will decrease the CO2 content and may be helpful in reducing global warming.