Search

A general method for the synthesis of so far unknown nonsymmetrically substituted N-aryl-N′-aryl′-4,4′-bipyridinium salts is presented (Scheme 1). The common intermediate in all procedures is N-(2,4-dinitrophenyl)-4,4′-bipyridinium hexafluorophosphate (1 ⋅ ). For the synthesis of nonsymmetric arylviologens, 1 ⋅ was arenamine-exchanged by the Zincke reaction, and then activated at the second bipyridine N-atom with 2,4-dinitrophenyl 4-methylbenzenesulfonate. The detailed preparation of the six N-aryl-N′-aryl′-viologens 21–26 is discussed (Scheme 2). The generality of the procedure is further exemplified by the synthesis of two nonsymmetrically substituted N-aryl-N′-benzyl- (see 11 and 12), and seven N-aryl-N′-alkyl-4,4′-bipyridinium salts (see 28–34) including substituents with metal oxide anchoring and redox tuning properties. The need for these compounds and their usage as electrochromic materials, in dendrimer synthesis, in molecular electronics, and in tunable-redox mediators is briefly discussed. The latter adjustable property is demonstrated by the reduction potential measured by cyclic voltammetry on selected compounds (Table).

An efficient time-domain reduced-order aeroelastic model is presented based on the Roger's state-space rational function approximation model and the frequency-domain Karhunen-Loeve method. Using frequency responses of the Roger's model, the method generates a real, orthogonal set of aeroelastic modes. These Karhunen-Loeve modes are optimal in the solution space with a minimum possible number of modes. When invoked with the Galerkin's error minimization, they generate a reduced-order aeroelastic model. The proposed method is demonstrated using an aeroelastic model of a representative commercial airplane with 638 state variables. It is shown that the aeroelastic results of the reduced-order model match extremely well the results obtained from the full-order model in both open-loop and closed-loop analyses. The new aeroelastic model can be efficiently used in repeated analysis of dynamic loads, optimization, and closed-loop designs.

Delta-like ligand 4 (Dll4), one of the Notch ligands, is overexpressed in ovarian cancer, especially in tumors resistant to anti-VEGF therapy. Here, we examined the biologic effects of dual anti-Dll4 and anti-VEGF therapy in ovarian cancer models. Using Dll4-Fc blockade and anti-Dll4 antibodies (murine REGN1035 and human REGN421), we evaluated the biologic effects of Dll4 inhibition combined with aflibercept or chemotherapy in orthotopic mouse models of ovarian cancer. We also examined potential mechanisms by which dual Dll4 and VEGF targeting inhibit tumor growth using immunohistochemical staining for apoptosis and proliferation markers. Reverse-phase protein arrays were used to identify potential downstream targets of Dll4 blockade. Dual targeting of VEGF and Dll4 with murine REGN1035 showed superior antitumor effects in ovarian cancer models compared with either monotherapy. In the A2780 model, REGN1035 (targets murine Dll4) or REGN421 (targets human Dll4) reduced tumor weights by 62% and 82%, respectively; aflibercept alone reduced tumor weights by 90%. Greater therapeutic effects were observed for Dll4 blockade (REGN1035) combined with either aflibercept or docetaxel (P < 0.05 for the combination vs. aflibercept). The superior antitumor effects of REGN1035 and aflibercept were related to increased apoptosis in tumor cells compared with the monotherapy. We also found that GATA3 expression was significantly increased in tumor stroma from the mice treated with REGN1035 combined with docetaxel or aflibercept, suggesting an indirect effect of these combination treatments on the tumor stroma. These findings identify that dual targeting of Dll4 and VEGF is an attractive therapeutic approach. Mol Cancer Ther; 15(6); 1344–52. ©2016 AACR.

In this paper, we present an approach for extraction of texture features of underwater images using Robust Local Binary Pattern (RLBP) descriptor. The literature survey reveals that the texture parameters that remain constant for the scene patch for the whole underwater image sequence. Therefore, we proposed technique to extract the texture features and these features can be used for object recognition and tracking. The underwater images suffer from image blurring and low contrast and performance of feature extractors is very less if we employ directly. Thus, we propose a novel image enhancement technique which is combination of different individual filters such as homomorphic filtering, curvelet denoising and LBP based Diffusion. We employ DoG based feature detector, for each detected interest point, the texture description is extracted using RLBP feature descriptor. The proposed feature extraction technique is compared and evaluated extensively with well known feature extractors using datasets acquired in underwater environment.

This paper describes the programmed assembly in solution of Ag and Au nanocrystals. The approach adopted utilizes Ag and Au nanocrystals whose surfaces have been modified by the chemisorption of mixtures of 1-dodecanethiol with N,N‘-2,6-pyridinediylbis(mercapto undecamide) (II) and with 1,2-mercaptododecyl-1-uracil (III), respectively. It is established that these nanocrystals recognize and selectively bind each other by the formation of an array of three complementary hydrogen bonds in a nonpolar solvent. This is among the first examples of the programmed assembly in solution of mixed-metal nanocrystal aggregates. In addition, this aggregation of mixed-metal nanocrystal dispersions is shown to be accompanied by a significant change in the optical spectrum over time. Binding is followed at the molecular level by 1H NMR spectroscopy and at the macroscopic level by dynamic light scattering, UV-vis spectroscopy, and TEM.

Aqueous solvolyses of acyl derivatives of hydrates (water adducts) of anthracene and benzofuran yield carbocations which undergo competitive deprotonation to form the aromatic molecules and nucleophilic reaction with water to give the aromatic hydrates. Trapping experiments with azide ions yield rate constants k(p) for the deprotonation and k(H2O) for the nucleophilic reaction based on the "azide clock". Combining these with rate constants for (a) the H(+)-catalyzed reaction of the hydrate to form the carbocation and (b) hydrogen isotope exchange of the aromatic molecule (from the literature) yields pK(R) = -6.0 and -9.4 and pK(a) = -13.5 and -16.3 for the protonated anthracene and protonated benzofuran, respectively. These pK values may be compared with pK(R) = -6.7 for naphthalene hydrate (1-hydroxy-1,2-dihydronaphthalene), extrapolated to water from measurements by Pirinccioglu and Thibblin for acetonitrile-water mixtures, and pK(a) = -20.4 for the 2-protonated naphthalene from combining k(p) with an exchange rate constant. The differences between pK(R) and pK(a) correspond to pK(H2O), the equilibrium constant for hydration of the aromatic molecule (pK(H2O) = pK(R) - pK(a)). For naphthalene and anthracene values of pK(H2O) = +13.7 and +7.5 compare with independent estimates of +14.2 and +7.4. For benzene, pK(a) = -24.3 is derived from an exchange rate constant and an assigned value for the reverse rate constant close to the limit for solvent relaxation. Combining this pK(a) with calculated values of pK(H2O) gives pK(R) = -2.4 and -2.1 for protonated benzenes forming 1,2- and 1,4-hydrates, respectively. Coincidentally, the rate constant for protonation of benzene is similar to those for protonation of ethylene and acetylene (Lucchini, V.; Modena, G. J. Am. Chem Soc. 1990, 112, 6291). Values of pK(a) for the ethyl and vinyl cations (-24.8) may thus be derived in the same way as that for the benzenonium ion. Combining these with appropriate values of pK(H2O) then yields pK(R) = -39.8 and -29.6 for the vinyl and ethyl cations, respectively.

The phenomenon of the tail buffet is usually associated with high-angle-of-attack operations of a twin-tail aircraft. The unsteady pressures that result from the tail buffet, along with the aeroelastic coupling of the vertical tail structural assembly, cause vibrations of the empennage structural assembly. Such buffet-induced vibrations can shorten the fatigue life the empennage structure and limit the flight envelope of the aircraft due to the large amplitudes of the fin vibrations. Methods of alleviating the tail buffet-induced vibrations, by the use of smart structure concepts, is presented. Theoretical and experimental investigations were conducted to estimate and enhance the required control authority for tail buffet alleviation using piezoceramic-stack-based actuators. This was accomplished by designing an effective piezoelectric ceramic actuator assembly, developing procedures to place the sensors and actuators optimally on the vertical tail subassembly, designing controllers using acceleration feedback control concepts, and developing procedures to implement these controllers by using digital signal processor-based systems

Purpose: To investigate the mechanisms of chemotherapy resistance and developing strategies to enhance therapeutic responses in mucinous ovarian cancer (MOC). Experimental design: We carried out a kinome-based siRNA screen using human MOC to identify novel targets to enhance the efficacy of chemotherapy in MOC cell lines. In vitro and in vivo validation studies were carried out using MOC models. We specifically interrogated the role of PRKRA in MOC based on our screen results. Results: Among the 939 genes in the screen, we focused on PRKRA/PACT because it was one of the top 5 target genes that exhibited the greatest extent of synthetic lethality in the target gene-siRNA plus oxaliplatin group relative to the target gene-siRNA group. The combination of oxaliplatin plus siPRKRA treatment resulted in significantly reduced cell viability compared with oxaliplatin plus control siRNA in RMUG-L-ip1 or RMUG-S-ip1 MOC cells (p Conclusion: The PRKRA/PACT axis represents an important therapeutic opportunity in MOC for enhancing oxaliplatin efficacy. Citation Format: Takeshi Hisamatsu, Michael McGuire, Sherry Y. Wu, Rajesha Rupaimoole, Sunila Pradeep, Kyunghee Noh, Justyna Filant, Jean M. Hansen, Yasmin Lyons, Kshipra M. Gharpure, Archana S. Nagaraja, Lingegowda S. Mangala, Takashi Mitamura, Cristian Rodriguez-Aguayo, Geoffrey A. Bartholomeusz, Cristina Ivan, Ju-Seong Lee, Koji Matsuo, Michael Frumovitz, Kwong K. Wong, Gabriel Lopez-Berestein, Anil K. Sood. PRKRA/PACT expression promotes chemoresistance in mucinous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 473. doi:10.1158/1538-7445.AM2017-473

This paper deals with emission quality of diesel engine based on eco toxicological studies with different methods of environmental standard toxicity tests satisfy the Bharath and European emission norms. Based on the emission norms, Corn Oil Methyl Ester (COME) with diesel is tested in a compression ignition engine and the performance and combustion characteristics are discussed. The corn oil was esterified and the property of corn oil methyl ester was within the limits specified in ASTM D 6751-03. The COME was blended together with diesel in different proportion percentages along with B20, B40, B60, B80, and B100. The emission and performance tests for various blends of COME was carried out using single cylinder, four stroke diesel engine, and compared with the performance obtained with 100% diesel (D100). The results give clear information that COME has low exhaust emissions and increase in performance compared to D100 without any modifications. It gives better performance, which is nearer to the obtained results of D100. Specific Fuel Consumption (SFC) of B100 at the full load condition is found to be 4% lower than that of (D100). The maximum Brake Thermal Efficiency (BTE) of B100 is found to be 8.5% higher than that of the D100 at full load. Also, the maximum BTE of part load for different blends is varied from 5.9% to 7.45% which is higher than D100. The exhaust gas emissions like Carbon Monoxide (CO), Carbon Dioxide (CO2), Hydro Carbon (HC) and Nitrogen Oxide (NOx) are found to be 2.3 to 18.8% lower compared to D100 for part as well as full load. The heat release rate of biodiesel and it blends are found to 16% to 35% lower as compared to D100 for part load, where as for full load it is 21% lower than D100. The results showed that the test of emissions norms are well within the limits of Bharath VI and European VI and it leads to less pollution, less effect on green eco system and potential substitute to fossil fuels.

In this paper, we proposed a technique for representation of facial expression based on extraction of Robust Local Binary Pattern (RLBP) features in curvelet domain. The curvelet transform exhibit improved directional capability, better ability to represent edges and other singularities along curves as compared to traditional multiscale transform such as wavelet transform. Hence, we transform original face images to frequency domain at a specific scale and orientation using curvelet transform. Noise and illumination invariant features are extracted from approximate sub-band using robust local binary pattern, which forms the feature vector of facial expression. The proposed method is evaluated based on facial expression recognition carried out using a benchmark database such as JAFFE. The facial expression recognition is performed using a chi-square distance measure with a nearest neighbor classifier. Experimental results show that our approach outperforms other popular LBP based approaches.

Despite being among the most common oncogenes in human cancer, to date, there are no effective clinical options for inhibiting KRAS activity. We investigated whether systemically delivered KRAS siRNAs have therapeutic potential in KRAS-mutated cancer models. We identified KRAS siRNA sequences with notable potency in knocking down KRAS expression. Using lung and colon adenocarcinoma cell lines, we assessed antiproliferative effects of KRAS silencing in vitro. For in vivo experiments, we used a nanoliposomal delivery platform, DOPC, for systemic delivery of siRNAs. Various lung and colon cancer models were used to determine efficacy of systemic KRAS siRNA based on tumor growth, development of metastasis, and downstream signaling. KRAS siRNA sequences induced >90% knockdown of KRAS expression, significantly reducing viability in mutant cell lines. In the lung cancer model, KRAS siRNA treatment demonstrated significant reductions in primary tumor growth and distant metastatic disease, while the addition of CDDP was not additive. Significant reductions in Ki-67 indices were seen in all treatment groups, whereas significant increases in caspase-3 activity were only seen in the CDDP treatment groups. In the colon cancer model, KRAS siRNA reduced tumor KRAS and pERK expression. KRAS siRNAs significantly reduced HCP1 subcutaneous tumor growth, as well as outgrowth of liver metastases. Our studies demonstrate a proof-of-concept approach to therapeutic KRAS targeting using nanoparticle delivery of siRNA. This study highlights the potential translational impact of therapeutic RNA interference, which may have broad applications in oncology, especially for traditional “undruggable” targets. Mol Cancer Ther; 13(12); 2876–85. ©2014 AACR.

Purpose Bisphosphonates have been shown to inhibit and deplete macrophages. The effects of bisphosphonates on other cell types in the tumor microenvironment have been insufficiently studied. Here, we sought to determine the effects of bisphosphonates on ovarian cancer angiogenesis and growth via their effect on the microenvironment, including macrophage, endothelial and tumor cell populations. Experimental Design Using in vitro and in vivo models, we examined the effects of clodronate on angiogenesis and macrophage density, and the overall effect of clodronate on tumor size and metastasis. Results Clodronate inhibited the secretion of pro-angiogenic cytokines by endothelial cells and macrophages, and decreased endothelial migration and capillary tube formation. In treated mice, clodronate significantly decreased tumor size, number of tumor nodules, number of tumor-associated macrophages and tumor capillary density. Conclusions Clodronate is a potent inhibitor of tumor angiogenesis. These results highlight clodronate as a potential therapeutic for cancer.

A numerical and experimental study on performance and emission characteristics of four-stroke, four-cylinder Multi Point Injection (MPI) engine operating on iso-butanol/gasoline blends was carried out. The study aims at extending the widely used Wiebe function to combustion modeling of alternate fuels. Quasi one-dimensional simulation and experiments were carried out for different blends of iso-butanol and gasoline (0% (pure gasoline), 10% (IB10), 20% (IB20), 30% (IB30), by volume of iso-butanol) at wide open throttle (WOT) condition for five engine speeds in the range of 2000 to 4000 rpm. The computational and experimental results complement each other validating the proposed extension. BSFC of the blends initially drops for IB10 and later rises with increase in concentration of iso-butanol. Compared to gasoline, the blends lead to considerable decrease in the amount of unburned hydrocarbons (HC) and no change of carbon monoxide (CO). However, there is considerable increase in the amount of oxides of nitrogen (NOx).

Described is the preparation of transparent nanostructured TiO2 (anatase) and Sb-doped SnO2 films supported on F-doped conducting glass. Also described is the modification of these films by chemiso...

A micro-controller-based retort control system for sterilization of foods was developed. The feature of this developed control system is that actual container cold point temperature is sensed on real time basis using temperature sensors. The on-line temperature is further processed using software to determine the sterilization value in terms of F o and is continuously displayed. The sterilization process is controlled until the set F o value is attained and at the end of the heating process cooling is automatically started. This ensures commercial sterility leading to higher nutrient retention and savings in energy by avoiding overcooking. This system can be easily incorporated onto the existing manually controlled batch retorts – horizontal or vertical. The system is more economical than the large sophisticated computer controlled systems presently available. It is mainly aimed at small and medium scale food processing industries having manually operated batch retorts.

Photoelectrochemical studies were carried out on [MnMoO2(NCS)(Ox)3(H2O)2] {Ox=8-quinolinol} complex in aqueous dimethylformamide medium in a Honda cell. The system developed a maximum potential of 335 mV when exposed to visible light at 30°C and was found to be reversible. The photogalvanic behaviour has been further investigated by varying the pH, temperature and photosensitizers. When a temperature difference between the illuminated and dark half-cells was maintained, the system generated 410 mV at 60°C. A solid-state galvanic cell, developed using the complex mixed with tetraethylammonium perchlorate (TEAP), showed a maximum voltage of 25 mV. A sandwich galvanic cell, constructed from transparent tin oxide-glass/complex/platinum, developed a maximum photovoltage of 88 mV when irradiated with a tungsten halogen lamp. Copyright © 2000 John Wiley & Sons, Ltd.

Near size-monodisperse silver nanocrystals stabilized by chemisorption of a mixture of an alkane thiol (85%) and an alkane thiol incorporating a dibenzo-24-crown-8 moiety (15%) have been prepared. Using dynamic light scattering and nuclear magnetic resonance, it is shown that addition of bis-dibenzylammonium dication initiates aggregation of the silver nanocrystal dispersion by pseudorotaxane assembly. It is also shown that addition of excess dibenzylammonium cation or dibenzo-24-crown-8 inhibits further aggregation. This novel demonstration of controlled nanocrystal aggregation points the way toward the programmed assembly of complex nanocrystal architectures in solution.

Size monodisperse silver nanocrystals have been stabilized by chemisorption of long-chain alkane thiols incorporating a receptor site. When dispersed in a suitable solvent these nanocrystals recogn...

This paper describes the preparation of an aqueous dispersion of electrostatically stabilized gold nanocrystals. It also describes the characterization of these nanocrystals by NMR, SAXS, SLS, and ...

Gold nanocrystals, stabilized by thiols covalently bound to a dibenzo[24]crown-8 moiety, have been programmed to recognize and selectively bind dibenzylammonium cations in solution. This results in a self-organization process at the surface of a nanocrystal with the assembly of a pseudorotaxane (see picture).

Gold-Nanokristalle, stabilisiert durch Thiole, die kovalent mit einer Kronenethereinheit verbunden sind, wurden auf das Erkennen und die selektive Bindung von Dibenzylammoniumionen in Losung programmiert. Das Ergebnis ist ein Selbstorganisationsprozes an der Nanokristalloberflache unter Bildung eines Pseudorotaxans (siehe Bild).

Manganese–molybdenum–diethyldithiocarbamate [MnMoO2(Et2dtc)4(H2O)] {Et2dtc=diethyldithiocarbamate} complex has exhibited reversible photogalvanic behaviour in aqueous dimethylformamide medium when studied in a Honda cell. The photogalvanic behaviour has been further investigated by varying the pH, temperature and photosensitizers. UV, visible and sunlight were used as the radiation sources. A maximum potential of 345 mV was obtained at 80°C in visible light. The system was found to be reversible for several cycles. A photoelectrochemical cell was constructed by coupling a charged nickel electrode with the complex electrode which incorporates the experimental compound in acetylene black on a nickel substrate. A maximum potential of 1·08 V with 80 μA current was obtained when irradiated with tungsten lamp. Copyright © 1999 John Wiley & Sons, Ltd.

Gold nanocrystals stabilized by a chemisorbed mixture of a long-chain alkane thiol, namely dodecanethiol (95%), and a long-chain dodecanethiol incorporating a receptor, namely 12-mercaptododecyl-1-uracil (5%), have been prepared. In solution, these nanocrystals recognize and selectively bind a long-chain alkane incorporating a complementary substrate, namely, N,N‘-2,6-pyridinediylbis[undecamide].

Heterobinuclear manganese-molybdenum complex with the Schiff base prepared by the condensation of diethylenetriamine with salicylaldehyde yielded a polymeric mixed metal coordination complex with the composition of [Mn1·5MoO3L]. The infrared spectral data indicated the presence of azomethine (HC=N) and Mo=O groups.1H NMR further confirmed the coordination of azomethine nitrogen and absence of phenolic hydrogen. The EPR studies suggested the presence of Mn(II) in the complex. The solid state conductivity studies with the variation of potential and temperature indicated a specific conductivity of 1·6×10−5 ohm−1 cm−1. The activation energy was found to be 0·019 eV. Hall measurements indicate that the material isp-type which is further confirmed by iodine doping which increases the conductivity by two orders of magnitude.

Piperazine-1,4-diium bis 2,4,6-trinitrophenolate is one of the useful organic materials with nonlinear optical (NLO) and pharmaceutical applications. The material was grown by slow evaporation solution growth method at room temperature. The crystal system and lattice parameters were identified by single crystal XRD analysis. The grown material crystallizes in monoclinic system with P21/n space group. The main functional groups NH2, NO2, CN, CC, and phenolic 'O' atom were identified using FTIR analysis. The protons and carbons of grown crystal with various chemical environments were studied by 1H and 13C NMR spectroscopy to confirm the molecular structure. The optical properties of the crystal were studied by UV-vis-NIR spectroscopy and the transmission 100% range starts from 532 nm onwards. The optical band gap was measured as 2.63 eV from the plot of (αhν)2 versus hν. The thermal stability was detected at 304.1°C using TG-DTA analysis. The dielectric studies of the sample were carried out at different temperatures in the frequency range from 50 Hz to 5 MHz to establish the dielectric nature of the crystal. Photoconductivity measurements were carried out on the grown crystal. The Second Harmonic Generation (SHG) of the crystal was tested to confirm the nonlinear optical property.

Cancer-related deregulation of miRNA biogenesis has been suggested, but the underlying mechanisms remain elusive. Here we report a previously unrecognized effect of hypoxia in the downregulation of Drosha and Dicer in cancer cells that leads to dysregulation of miRNA biogenesis and increased tumour progression. We show that hypoxia-mediated downregulation of Drosha is dependent on ETS1/ELK1 transcription factors. Moreover, mature miRNA array and deep sequencing studies reveal altered miRNA maturation in cells under hypoxic conditions. At a functional level, this phenomenon results in increased cancer progression in vitro and in vivo, and data from patient samples are suggestive of miRNA biogenesis downregulation in hypoxic tumours. Rescue of Drosha by siRNAs targeting ETS1/ELK1 in vivo results in significant tumour regression. These findings provide a new link in the mechanistic understanding of global miRNA downregulation in the tumour microenvironment.

A TiO2 nanocrystallite has been modified to selectively bind, by complementary hydrogen bonding, a uracil substrate incorporating a viologen moiety. Bandgap excitation of the self-assembled donor (TiO2 nanocrystallite)−acceptor (viologen) complex results in electron transfer. Some implications of these findings for the self-assembly of functional nanostructures containing both condensed phase and molecular components are considered.

TiO2 nanocrystallites are prepared by hydrolysis of titanium tetraisopropoxide in the presence of N,N‘-2,6-pyridinediylbis[undecamide]. The latter stabilizes the resulting semiconductor sol and pro...

Platinum compounds display clinical activity against a wide variety of solid tumors; however, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. We found that ATP11B expression was correlated with higher tumor grade in human ovarian cancer samples and with cisplatin resistance in human ovarian cancer cell lines. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-targeted siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux kinetics indicated that ATP11B enhances the export of cisplatin from cells. The colocalization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins, such as syntaxin-6 (STX6) and vesicular-associated membrane protein 4 (VAMP4), strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, inhibition of ATP11B expression could serve as a therapeutic strategy to overcome cisplatin resistance.

Improving small interfering RNA (siRNA) efficacy in target cell populations remains a challenge to its clinical implementation. Here, we report a chemical modification, consisting of phosphorodithioate (PS2) and 2'-O-Methyl (2'-OMe) MePS2 on one nucleotide that significantly enhances potency and resistance to degradation for various siRNAs. We find enhanced potency stems from an unforeseen increase in siRNA loading to the RNA-induced silencing complex, likely due to the unique interaction mediated by 2'-OMe and PS2. We demonstrate the therapeutic utility of MePS2 siRNAs in chemoresistant ovarian cancer mouse models via targeting GRAM domain containing 1B (GRAMD1B), a protein involved in chemoresistance. GRAMD1B silencing is achieved in tumours following MePS2-modified siRNA treatment, leading to a synergistic anti-tumour effect in combination with paclitaxel. Given the previously limited success in enhancing siRNA potency with chemically modified siRNAs, our findings represent an important advance in siRNA design with the potential for application in numerous cancer types.

Nature Communications 4: Article number: 1403 (2013); Published: 29 January 2013; Updated: 29 July 2013. The original version of this Article contained a typographical error in the spelling of the author Mian M. K. Shahzad, which was incorrectly given as Mian M. K. Shazhad. This has now been corrected in both the PDF and HTML versions of the Article.

Linked viologen-anthraquinone molecules are attached to TiO2 nanocrystallites supported on a conducting glass substrate. The resulting assembly is incorporated as the working electrode in an electrochemical cell. Under opencircuit conditions, band-gap excitation of the semiconductor nanocrystallite results in viologen-mediated electron transfer to anthraquinone. Prior application of a negative potential step, which results in 2e−/2H+ reduction of anthraquinone, permits electron transfer only to viologen. At positive applied potentials, electron transfer following band-gap excitation is largely suppressed. Some implications of these findings for modulation of function in molecular devices are considered.

Background: Schizophrenia is a disorder of relatively high point prevalence, low incidence and high disability. It accounts for nearly 1.5-3% of total national expenditure on health care. There is a gross variation in the cost of various branded and generic versions of antipsychotics available in India. This can lead to decreased patient compliance. The present study was undertaken to highlight this variation in the cost of various preparations of antipsychotics (branded and generic) available in India.Methods: Cost ratio and Percentage variation in cost of various antipsychotics available were calculated by standard formulae and analysed.Results: There is a very high variation in the cost of various antipsychotics available in India. The highest variation in cost ratio was seen with risperidone 2mg, 3mg and olanzapine 10mg, while the highest percentage cost variation was seen with risperidone 3mg, 4mg, 1mg; olanzapine 2.5mg, 5mg, 50mg, 100mg; levosulpiride 25mg and chlorpromazine 20mg. The lowest percentage cost variation was seen with Flupenthixol 3mg and Amisulpiride 300mg.Conclusions: There is a definite need to further strengthen the Drug Price Regulatory Mechanisms with regard to antipsychotics available in India in order to improve the patient compliance and thus cure rates of this burdensome and costly illness.