Asymptotic wavenumber expansions of a strongly orthotropic fluid-filled circular cylindrical shell

In this paper, a suitable nondimensional `orthotropy parameter' is defined and asymptotic expansions are found for the wavenumbers in in vacuo and fluid-filled orthotropic circular cylindrical shells modeled by the Donnell-Mushtari theory. Here, the elastic moduli in the two directions are greatly different; the particular case of E-x >> E-theta is studied in detail, i.e., the elastic modulus in the longitudinal direction is much larger than the elastic modulus in the circumferential direction. These results are compared with the corresponding results for a `slightly orthotropic' shell (E-x approximate to E-theta) and an isotropic shell. The novelty of this presentation lies in obtaining closed-form expansions for the in vacuo and coupled wavenumbers in an orthotropic shell using perturbation methods aiding in a better physical understanding of the problem.

A novel DNA intercalator, 8-methoxy pyrimido4 `,5 `:4,5]thieno (2,3-b)quinoline-4(3H)-one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor

Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause any major side effects as observed upon hematological and serum profiling. We also found that MPTQ induces cytotoxicity in cancer cell lines, by activating apoptosis both by intrinsic and extrinsic pathways. Thus, MPTQ could be used as a potential cancer therapeutic agent.

Durability of Pt/C and Pt/MC-PEDOT catalysts under simulated start-stop cycles in polymer electrolyte fuel cells

A composite of mesoporous carbon (MC) with poly(3,4-ethylenedioxythiophene) (PEDOT) is studied as catalyst support for platinum nanoparticles. The durability of commercial Pt/carbon and Pt/MC-PEDOT as cathode catalyst is investigated by invoking air-fuel boundary at the anode side so as to foster carbon corrosion at the cathode side of a polymer electrolyte fuel cell (PEFC). Pt/MC-PEDOT shows higher resistance to carbon corrosion in relation to Pt/C. Electrochemical techniques such as cyclic voltammetry (CV) and impedance measurements are used to evaluate the extent of degradation in the catalyst layer. It is surmised that the resistance of MC-PEDOT as catalyst support toward electrochemical oxidation makes Pt/MC-PEDOT a suitable and stable cathode catalyst for PEFCs.

IGF-1 stimulated upregulation of cyclin D1 is mediated via STAT5 signaling pathway in neuronal cells

Signal Transducer and Activator of Transcription (STATs) regulate various target genes such as cyclin D1, MYC, and BCL2 in nonneuronal cells which contribute towards progression as well as prevention of apoptosis and are involved in differentiation and cell survival. However, in neuronal cells, the role of STATs in the activation and regulation of these target genes and their signaling pathways are still not well established. In this study, a robust cyclin D1 expression was observed following IGF-1 stimulation in SY5Y cells as well as neurospheres. JAK/STAT pathway was shown to be involved in this upregulation. A detailed promoter analysis revealed that the specific STAT involved was STAT5, which acted as a positive regulatory element for cyclin D1 expression. Overexpression studies confirmed increase in cyclin D1 expression in response to STAT5a and STAT5b constructs when compared to dominant-negative STAT5. siRNA targeting STAT5, diminished the cyclin D1 expression, further confirming that STAT5 specifically regulated cyclin D1 in neuronal cells. Together, these findings shed new light on the mechanism of IGF-1 mediated upregulation of cyclin D1 expression in neural cell lines as well as in neural stem cells via the JAK/STAT5 signaling cascade.

The precision with which single cells of Dictyostelium discoideum can locate a source of cyclic AMP

When stimulated by a point source of cyclic AMP, a starved amoeba of Dictyostelium discoideum responds by putting out a hollow balloon-like membrane extension followed by a pseudopod. The effect of the stimulus is to influence the position where either of these protrusions is made on the cell rather than to cause them to be made. Because the pseudopod forms perpendicular to the cell surface, its location is a measure of the precision with which the cell can locate the cAMP source. Cells beyond 1 h of starvation respond non-randomly with a precision that improves steadily thereafter. A cell that is starved for 1-2 h can locate the source accurately 43% of the time; and if starved for 6-7 h, 87% of the time. The response always has a high scatter; population-level heterogeneity reflects stochasticity in single cell behaviour. From the angular distribution of the response its maximum information content is estimated to be 2-3 bits. In summary, we quantitatively demonstrate the stochastic nature of the directional response and the increase in its accuracy over time.

Investigation of phase separation in bulk heterojunction solar cells via supramolecular chemistry

In this work, we have prepared two donor-acceptor-donor (D-A-D) pi-conjugated oligomers to investigate the effect of phase separation on the performance of bulk heterojunction (BHJ) solar cells. These charge transfer low band gap pi-conjugated oligomers (TTB and NMeTTB) were synthesized by Knoevenagel condensation of terthiophenecarbaldehyde and barbiturate appended pyran derivative. The thin film morphology of both the oligomers and along with electron acceptor 6,6]-phenyl-C60-butyric acid methyl ester (PC61BM) was investigated by atomic force microscopy (AFM) and transmission electron microscopy (TEM). The blend of NMeTTB and PC61BM thin film yield highly ordered thin film, whereas there was clear phase separation between TTB and PC61BM in thin film. The BHJ solar cell was fabricated using a blend of NMeTTB and TTB with PC61BM acceptor in 1:1 ratio as active layer, and a power conversion efficiency of 1.8% was obtained. This device characteristic was compared with device having TTB:PC61BM as active layer, and large difference is observed in photocurrents. This poor performance of TTB in BHJ devices was attributed to the difference in the nanoscale morphology of the corresponding derivatives. We rationalize our findings based on the low charge carrier mobility in organic field-effect transistors and miscibility/phase separation parameter of binary components (oligomers and PC61BM) in the active layer of bulk heterojunction solar cells.

Intracellular reactive oxidative stress, cell proliferation and apoptosis of Schwann cells on carbon nanofibrous substrates

Despite considerable research to develop carbon based materials for biomedical applications, the toxicity of carbon remains a major concern. In order to address this issue as well as to investigate the cell fate processes of neural cells from the perspective of neural tissue engineering applications, the in vitro cytocompatibility of polyacrylonitrile (PAN) derived continuous carbon nanofibers and PAN derived carbon thin films were investigated both quantitatively and qualitatively using in vitro biochemical assays followed by extensive flow cytometry analysis. The experimental results of Schwann cell fate, i.e. cell proliferation, cell metabolic activity and cell apoptosis on amorphous carbon substrates are discussed in reference to the time dependent evolution of intracellular oxidative stress. Apart from providing evidence that an electrospun carbon nanofibrous substrate can physically guide the cultured Schwann cells, this study suggested that continuous carbon nanofibers and amorphous carbon films are not cytotoxic in vitro and do not significantly induce apoptosis of Schwann cells, but in fact even facilitate their proliferation and growth.

Channel II photocurrent quantification in narrow optical gap polymer-fullerene solar cells with complimentary acceptor absorption

Most charge generation studies on organic solar cells focus on the conventional mode of photocurrent generation derived from light absorption in the electron donor component (so called channel I). In contrast, relatively little attention has been paid to the alternate generation pathway: light absorption in the electron acceptor followed by photo-induced hole transfer (channel II). By using the narrow optical gap polymer poly(3,6-dithieno3,2-b] thiophen-2-yl)-2,5-bis(2-octyldodecyl)-pyrrolo- 3,4-c]pyrrole-1,4-dione-5',5 `'-diyl-alt-4,8-bis(dodecyloxy) benzo1,2-b:4,5-b'] dithiophene-2,6-diyl with two complimentary fullerene absorbers; phenyl-C-61-butyric acid methyl ester, and phenyl-C-71-butyric acid methyl ester (70-PCBM), we have been able to quantify the photocurrent generated each of the mechanisms and find a significant fraction (>30%), which is derived in particular from 70-PCBM light absorption.

Pulsed electric field mediated in vitro cellular response of fibroblast and osteoblast-like cells on conducting austenitic stainless steel substrate

This article reports the intermittent pulse electric field stimulus mediated in vitro cellular response of L929 mouse fibroblast/SaOS2 osteoblast-like cells on austenitic steel substrates in reference to the field strength dependent behavior. The cellular density and morphometric analyses revealed that the optimal electric (E) fields for the maximum cell density of adhered L929 (similar to 270 % to that of untreated sample) and SaOS2 (similar to 280 % to that of untreated sample) cells are 1 V (0.33 V/cm) and 2 V (0.67 V/cm), respectively. The trend in aspect ratio of elongated SaOS2 cells did not indicate any significant difference among the untreated and treated (up to 3.33 V/cm) cells. The average cell and nucleus areas (for SaOS2 cells) were increased with an increase in the applied voltage up to 8 V (2.67 V/cm) and reduced thereafter. However, the ratio of nucleus to total cell area was increased significantly on the application of higher voltages (2-10 V), indicating the possible influence of E-field on cell growth. Further, the cell density results were compared with earlier results obtained with sintered Hydroxyapatite (HA) and HA-BaTiO3 composites and such comparison revealed that the enhanced cell density on steel sample occurs upon application of much lower field strength and stimulation time. This indicates the possible role of substrate conductivity towards cell growth in pulsed E-field mediated culture conditions.

Determination of electric field at and near the focus of a cylindrical lens for applications in fluorescence microscopy

We present an explicit computable integral solution of the electric field generated at the focal region of a cylindrical lens. This representation is based on vectorial diffraction theory and further enables the computation of the system point spread function of a cylindrical lens. It is assumed that there is no back-scattering and the contribution from the evanescent field is negligible. Stationary phase approximation along with the Fresnel transmission coefficients are employed for evaluating the polarization dependent electric field components. Studies were carried out to determine the polarization effects and to calculate the system resolution. The effect of s -, p - and randomly polarized light is studied on the fixed sample (electric dipole is fixed in space). Proposed approach allows better understanding of electric field effects at the focus of a cylindrical aplanatic system. This opens up future developments in the field of fluorescence microscopy and optical imaging. (C) 2013 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.

Asymptotic expansions for the structural wavenumbers of isotropic and orthotropic fluid-filled circular cylindrical shells in the intermediate frequency range

We consider wavenumbers in in vacuo and fluid-filled isotropic and orthotropic shells. Using the Donnell-Mushtari (DM) theory we find compact and elegant asymptotic expansions for the wavenumbers in the intermediate frequency range, i.e., around the ring frequency. This frequency range corresponds to the frequencies where there is a rapid change in the values of bending wavenumbers and is found to exist in isotropic and orthotropic shells (in vacua and fluid-filled) for low circumferential orders n only. The same is first identified using the n=0 mode of an orthotropic shell. Following this, using the expression for the intermediate frequency, asymptotic expansions are found for other cases. Here, in order to get compact expansions we consider slight orthotropy (epsilon << 1) and light fluid loading (mu << 1). Thus, the orthotropy parameter epsilon and the fluid loading parameter mu are used as asymptotic parameters along with the non-dimensional thickness parameter beta. The methodology can be extended to any order of epsilon, only the expansions become unwieldy. The expansions are matched with the numerical solutions of the corresponding dispersion relation. The match is found to be good.

CXI-benzo-84 reversibly binds to tubulin at colchicine site and induces apoptosis in cancer cells

Here, we have discovered CXI-benzo-84 as a potential anticancer agent from a library of benzimidazole derivatives using cell based screening strategy. CXI-benzo-84 inhibited cell cycle progression in metaphase stage of mitosis and accumulated spindle assembly checkpoint proteins Mad2 and BubR1 on kinetochores, which subsequently activated apoptotic cell death in cancer cells. CXI-benzo-84 depolymerized both interphase and mitotic microtubules, perturbed EB1 binding to microtubules and inhibited the assembly and GTPase activity of tubulin in vitro. CXI-benzo-84 bound to tubulin at a single binding site with a dissociation constant of 1.2 +/- 0.2 mu M. Competition experiments and molecular docking suggested that CXI-benzo-84 binds to tubulin at the colchicine-site. Further, computational analysis provided a significant insight on the binding site of CXI-benzo-84 on tubulin. In addition to its potential use in cancer chemotherapy, CXI-benzo-84 may also be useful to screen colchicine-site agents and to understand the colchicine binding site on tubulin. (C) 2013 Elsevier Inc. All rights reserved.

Propyl-2-(8-(3,4-Difluorobenzyl)-2 `,5 `-Dioxo-8-AzaspiroBicyclo3.2.1] Octane-3,4 `-Imidazolidine]-1 `-yl) Acetate Induces Apoptosis in Human Leukemia Cells through Mitochondrial Pathway following Cell Cycle Arrest

Background: Due to the functional defects in apoptosis signaling molecules or deficient activation of apoptosis pathways, leukemia has become an aggressive disease with poor prognosis. Although the majority of leukemia patients initially respond to chemotherapy, relapse is still the leading cause of death. Hence targeting apoptosis pathway would be a promising strategy for the improved treatment of leukemia. Hydantoin derivatives possess a wide range of important biological and pharmacological properties including anticancer properties. Here we investigated the antileukemic activity and mechanism of action of one of the potent azaspiro hydantoin derivative, (ASHD). Materials and Methods: To investigate the antileukemic efficacy of ASHD, we have used MTT assay, cell cycle analysis by FACS, tritiated thymidine incorporation assay, Annexin V staining, JC1 staining and western blot analysis. Results: Results showed that ASHD was approximately 3-fold more potent than the parent compounds in inducing cytotoxicity. Tritiated thymidine assay in conjunction with cell cycle analysis suggests that ASHD inhibited the growth of leukemic cells. The limited effect of ASHD on cell viability of normal cells indicated that it may be specifically directed to cancer cells. Translocation of phosphatidyl serine, activation of caspase 3, caspase 9, PARP, alteration in the ratio of BCL2/BAD protein expression as well as the loss of mitochondrial membrane potential suggests activation of the intrinsic pathway of apoptosis. Conclusion: These results could facilitate the future development of novel hydantoin derivatives as chemotherapeutic agents for leukemia.

Charge Injection through Nanocomposite Electrode in Microfluidic Channel for Electrical Lysis of Biological Cells

Several concepts have been developed in the recent years for nanomaterial based integrated MEMS platform in order to accelerate the process of biological sample preparation followed by selective screening and identification of target molecules. In this context, there exist several challenges which need to be addressed in the process of electrical lysis of biological cells. These are due to (i) low resource settings while achieving maximal lysis (ii) high throughput of target molecules to be detected (iii) automated extraction and purification of relevant molecules such as DNA and protein from extremely small volume of sample (iv) requirement of fast, accurate and yet scalable methods (v) multifunctionality toward process monitoring and (vi) downward compatibility with already existing diagnostic protocols. This paper reports on the optimization of electrical lysis process based on various different nanocomposite coated electrodes placed in a microfluidic channel. The nanocomposites are synthesized using different nanomaterials like Zinc nanorod dispersion in polymer. The efficiency of electrical lysis with various different electrode coatings has been experimentally verified in terms of DNA concentration, amplification and protein yield. The influence of the coating thickness on the injection current densities has been analyzed. We further correlate experimentally the current density vs. voltage relationship with the extent of bacterial cell lysis. A coupled multiphysics based simulation model is used to predict the cell trajectories and lysis efficiencies under various electrode boundary conditions as estimated from experimental results. Detailed in-situ fluorescence imaging and spectroscopy studies are performed to validate various hypotheses.

Aza-induced cardiomyocyte differentiation of P19 EC-cells by epigenetic co-regulation and ERK signaling

Stem cells in cell based therapy for cardiac injury is being potentially considered. However, genetic regulatory networks involved in cardiac differentiation are not clearly understood. Among stem cell differentiation models, mouse P19 embryonic carcinoma (EC) cells, are employed for studying (epi)genetic regulation of cardiomyocyte differentiation. Here, we comprehensively assessed cardiogenic differentiation potential of 5-azacytidine (Aza) on P19 EC-cells, associated gene expression profiles and the changes in DNA methylation, histone acetylation and activated-ERK signaling status during differentiation. Initial exposure of Aza to cultured EC-cells leads to an efficient (55%) differentiation to cardiomyocyte-rich embryoid bodies with a threefold (16.8%) increase in the cTnI(+) cardiomyocytes. Expression levels of cardiac-specific gene markers i.e., Isl-1, BMP-2, GATA-4, and alpha-MHC were up-regulated following Aza induction, accompanied by differential changes in their methylation status particularly that of BMP-2 and alpha-MHC. Additionally, increases in the levels of acetylated-H3 and pERK were observed during Aza-induced cardiac differentiation. These studies demonstrate that Aza is a potent cardiac inducer when treated during the initial phase of differentiation of mouse P19 EC-cells and its effect is brought about epigenetically and co-ordinatedly by hypo-methylation and histone acetylation-mediated hyper-expression of cardiogenesis-associated genes and involving activation of ERK signaling.