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Improvement of bone microarchitecture in methylprednisolone induced rat model of osteoporosis by using thiolated chitosan-based risedronate mucoadhesive film
No full textObjective: In this study, we investigated the potential of thiolated chitosan-based mucoadhesive film, loaded with risedronate sodium in the treatment of osteoporosis. Significance: Risedronate sodium is a bisphosphonate derivative having very low bioavailability when administered through the oral route. Moreover, the adverse effects associated with the drug when administered through GIT necessitate an alternative and feasible route which can improve its bioavailability and therapeutic efficacy. Methods: Thiolation of chitosan was interpreted by different analytical techniques. The mucoadhesive films were prepared by the solvent evaporation method and evaluated for drug content analysis, swelling degree, mucoadhesive parameters, and permeation characterization. For the screening of preclinical efficacy and pharmacodynamic parameters, a methylprednisolone induced osteoporotic rat model was used. The trabecular microarchitecture and biochemical markers were evaluated for determination of bone resorption. Results: The different analytical characterization of synthesized thiolated chitosan revealed that chitosan was successfully incorporated with thiol groups. The formulation containing 2:1 ratio of thiolated chitosan and HPMC-4KM was found to have the maximum swelling degree, mucoadhesive strength with a good force of adhesion and better in vitro permeability compared to the marketed formulation. With respect to trabecular microarchitecture, the drug-loaded film formulation showed superior and promising results. Furthermore, the film formulation also improved the serum level of biomarkers better than the marketed formulation. Conclusions: The results significantly suggest that risedronate loaded novel mucoadhesive film formulation could be a logical approach in the therapeutic intervention of osteoporosis
Deformation field in deep flat punch indentation and the persistence of dead-metal zones
No full textThe indentation of metal by a flat punch is a model system for forming processes and intimately linked with hardness testing. Here, we perform first-in-class, high-fidelity finite element (FE) simulations in an arbitrary Lagrangian-Eulerian (ALE) framework to study the deformation field in deep punch indentation of annealed copper. The use of ALE allows indentation depth to punch width ratios as high as 1.6, while the use of Lagrangian tracer particles reveals pathlines of material transport. Field quantities such as the plastic strain, strain rate and velocity are obtained at high resolution. A low-strain, dead-metal zone (DMZ) that is stationary with respect to the indenter forms immediately below the punch. Crucially, it is found that DMZs are unavoidable in deep punch indentation, forming at the outset and irrespective of the coefficient of friction. However, the area of this zone shrinks as the indentation progresses at a rate that is inversely related to the friction. The simulations thus explain why Prandtl's view of punch indentation, which incorporates DMZs, is physically more accurate than Hill's view. The computations successfully reproduce the strain field inhomogeneity seen in recent in situ imaging experiments. While DMZ formation is impervious to the hardening model used, Zerilli-Armstrong hardening provides more accurate indentation force estimates than Johnson-Cook hardening. Lastly, the residual impression and factors affecting its shape are studied. The sides of impressed metal are never vertical, but at an inclination to it. Methods to modify such features, of potential interest in metal forming, are discussed briefly
Complex interactions underpin social behaviour in Dictyostelium giganteum
No full textIn the wild, social groups of the cellular slime mould amoeba Dictyostelium giganteum are genetically heterogeneous more often than not. When studied as 1:1 binary mixes, amoebae of one strain almost always form more spores than the other, an observation that leads one to wonder what might be responsible for the long-term persistence of different strains in nature. We have monitored a number of individual and collective traits bearing on reproductive fitness in chimaeras of Dictyostelium giganteum obtained by mixing pairs of starved amoebae belonging to distinct wild-type strains in proportions ranging from 1:9 to 9:1. The main findings are that intercellular interactions take place at more than one stage of the life cycle and that generalisations drawn after mixing cells only in a 1:1 ratio can be misleading. A strain that does better than another in respect of some component of fitness (for example, spore formation) may do worse in respect of a different component (for example, growth rate). Also, a strain that is a more efficient sporulator than a second strain in one context may be less efficient in another context. In addition to such trade-offs, spore formation in chimaeras can exhibit negative frequency dependence, which too can lead to stable co-existence.Significance statementHumans live in social groups whose members perform different but equally important tasks. When they do so freely, the long-term stability of the group depends on give and take (trade-offs') between individuals who are generally unrelated. In contrast, studies of cooperation in non-human animals have focussed on relatedness through common descent as responsible for the maintenance of group cohesion. But animal groups too contain unrelated individuals. Using the example of a social amoeba, we show that this need not rule out a high level of cooperation including so-called altruism, as long as inter-individual interactions permit it. In both genetically homogeneous and heterogeneous groups, interactions can result in trade-offs between different traits. In genetically heterogeneous groups, they can also lead to a negative correlation between the efficiency with which cells of a genotype reproduce and the proportion of cells belonging to that genotype
17 beta-estradiol potentiates TREK1 channel activity through G protein-coupled estrogen receptor
No full textTWIK-related potassium channel 1 (TREK1), a two-pore domain potassium channel, is modulated by various hormones and neurotransmitters by activation of membrane receptor - coupled second messengers. 17 beta-estradiol is a neuromodulator capable of regulating several cellular processes including the activity of ion channels, in a rapid and non-genomic manner. The G protein-coupled estrogen receptor (GPER) is known to facilitate rapid actions of 17 beta-estradiol, though its role in modulation of ion channels is not widely explored. Several studies have shown both TREK1 and 17 beta-estradiol to be neuromodulatory but the interaction between them is not known. In the present study, using single channel cell-attached patch clamp electrophysiology in HEK293 cells, we show that 17 beta-estradiol increases the activity of hTREK1 channel by acting through hGPER and increasing the channel opening probability within minutes. The potentiation induced by 17 beta-estradiol is pertussis toxin sensitive involving action of G beta gamma), subunits while the inhibitory effect of cAMP-PKA pathway on TREK1 is reduced. Protein phosphatases were also found to be important for the action of 17 beta-estradiol, which in concert with reduced activity of PKA, may alter the phosphorylation state of the channel and thus increase channel activity. Mutational studies revealed the serines at positions 315 and 348 in the C-terminal domain of hTREK1 to be the target sites for dephosphorylation induced by 17 beta-estradiol action through hGPER. Elucidation of the pathway for the potentiating action of 17 beta-estradiol via hGPER on hTREK1 channel activity will help us understand better one of the many possible neuroprotective mechanisms of 17 beta-estradiol and hTREK1 channel
Iodine-Catalyzed Chemoselective C-N Bond-Forming Reactions Using Benzylic or Cinnamyl Alcohols with Heterocyclic Thiols and Thiones
No full textA chemoselective formation of C-N bond catalyzed by iodine has been developed using heterocyclic thiols and thiones. The reaction occurs at the nitrogen center over the sulfur, leading to the amination against the traditional sulfenylation. A wide variety of allylic and benzylic alcohols serve as coupling partners. This method showed a good tolerance toward 1H-tetrazole-5-thiol, 5-methyl-1,3,4-thiadiazole-2-thiol, benzod]thiazole-2(3H)-thione, and benzod]oxazole-2(3H)-thione derivatives
Magnetic properties of superparamagnetic, nanocrystalline cobalt ferrite thin films deposited at low temperature
No full textBulk cobalt ferrite, being a hard ferrite, shows high magnetization, high resistivity and high coercivity. If thin films of cobalt ferrite can be deposited at a low enough temperature and if its coercivity can be reduced, cobalt ferrite will make a very good candidate for use as a magnetic core of an integrated inductor in RF-CMOS ICs. Though polycrystalline and epitaxial thin films of cobalt ferrite have been made by various techniques, there are no reports of thin films of superparamagnetic cobalt ferrite. In this work, nanocrystalline cobalt ferrite thin films, which are superparamagnetic as deposited, have been prepared in the solution medium at similar to 190 degrees C, using microwave irradiation. The as-prepared films have a saturation magnetization (MS) of 401 emu/cc and coercivity (H-C) of 19 Oe at room temperature for a crystallite size of 2 nm. The cobalt ferrite powder obtained as a byproduct during the same process has M-S of 50 emu/g and H-C of 5 Oe at room temperature, making it superparamagnetic. The as-prepared films were annealed in air at 300 degrees C for 5 min and 10 min. Annealing for 10 min results in an increase in crystallite size to 36 nm, MS increases from 401 emu/cc to 545 emu/cc, and H-C increases from 19 Oe to 860 Oe. The change in magnetic properties can be directly associated with change in the crystallite size and degree of crystallographic inversion, as determined by neutron diffraction and deduced from X-ray photoelectron spectroscopy
Designing Assembly of Meshes Having Diverse Wettability for Reducing Liquid Ejection at Terminal Velocity Droplet Impact
No full textIn this paper, we have studied the effect of surface wettability and geometrical parameters on the velocity of the ejecting jet during droplet impacts on meshes. This paper presents detailed experiments and modeling which helps in explaining a previous demonstration, where an assembly of meshes with different wettabilities was used to significantly reduce the amount of liquid leakage during impact of droplets travelling at terminal velocity. Drop impact on meshes at various Weber numbers (We) was captured using high-speed imaging. At higher We, the velocity of the ejected liquid jet (V-j) was found to be higher than the velocity of the impacting droplet (V-d) for most of the superhydrophobic meshes. In contrary, for all values of We the velocity of the ejected liquid through superhydrophilic meshes was lower than the droplet velocity for all meshes. While jet width for superhydrophobic mesh was close to the pore opening dimension, in case of superhydrophilic mesh merging of the ejected jets meant that the width was close to the impacting droplet diameter. A combination of superhydrophilic and superhydrophobic mesh was used to significantly reduce liquid ejection for droplet impact at terminal velocity (similar to 8 m/s). Less than 6 x 10(-5) % volume ejection was observed for the designed combination. This configuration can be used to fabricate rain repellent air-transparent surfaces
Scaling a Fluorescent Detection System by Polymer-Assisted 3-D Integration of Heterogeneous Dies
No full textScaling by 3-D integration of various heterogeneous components enables miniaturized systems. However, the heterogeneous system integration is challenging due to the dissimilarities in materials and process used in fabrication of individual components. In this paper, we demonstrate a simple 3-D integration method for miniaturization of systems. Various components of the system were stacked using SU-8-based planarization and epoxy-based bonding. Spacer dielectric (SU-8) was patterned using photolithography for the formation of interconnect vias. Electrical interconnects over the large topography between the layers was formed by the screen printing of silver nanoparticle epoxy. Using this integration technique, we demonstrate a fluorescence-sensing platform consisting of a silicon photodetector, plastic optical filters, commercial LED, and a glass microheater chip. This paper resolves several fabrication challenges of planarization, stacking, and interconnection of these divergent chips. For example, the process incompatibility of the plastic optical filters was resolved by additional passivation using parylene-C. The functionality of the demonstrated system is verified by detecting the fluorescence property of Rhodamine B and Rhodamine 6G dyes. Rhodamine B's sensitivity to temperature was also demonstrated using the on-chip microheater. This process flow can be scaled to stack a larger number of layers for demonstrations of more complicated systems with enhanced functionality and applications
SPARSE SUPPORT RECOVERY VIA COVARIANCE ESTIMATION
No full textWe consider the problem of recovering the common support of a set of k-sparse signals {X-i}(i=1)(L) from noisy linear under-determined measurements of the form {Phi X-i + w(i)}(i=1)(L) where Phi is an element of R-mxN (m < N) is the sensing matrix and w(i )is the additive noise. We employ a Bayesian setup where we impose a Gaussian prior with zero mean and a common diagonal covariance matrix Gamma across all x(i), and formulate the support recovery problem as one of covariance estimation. We develop an algorithm to find the approximate maximum-likelihood estimate of Gamma using a modified reweighted minimization procedure. Empirically, we find that the proposed algorithm succeeds in exactly recovering the common support with high probability in the k < m regime with L of the order of m and in the k >= m regime with larger L. The key advantage of the proposed algorithm is that its complexity is independent of L, unlike existing sparse support recovery algorithms
Performance Analysis of Full-Duplex Relaying with Media-Based Modulation
No full textIn this paper, we analyze the performance of a two-hop three-node full-duplex (FD) relay network, where the source and relay nodes transmit using media-based modulation (MBM). MBM is a promising new modulation scheme that conveys information bits by digitally controlling the parasitic elements (called as radio frequency mirrors) placed near the transmit antenna. The relay uses decode-and-forward relaying protocol. We refer to this system as FD relaying with MBM (FDR-MBM) system. First, we derive an upper bound on the end-to-end average bit error probability of FDR-MBM with maximum-likelihood (ML) detection at the relay and destination nodes. This bound is shown to be increasingly tight with increasing signal-to-noise ratio. Our numerical results show that, for the same spectral efficiency, FDR-MBM can perform better than FD relaying with conventional modulation schemes such as QAM/PSK. Next, we derive the diversity order achieved by the FDR-MBM system. Also, the analytically predicted diversity order is validated through simulations