Strong Potential Candidates Research Articles

Prenylated Flavonoids with Selective Toxicity against Human Cancers.

The antiproliferative activity of xanthohumol (1), a major prenylated chalcone naturally occurring in hops, and its aurone type derivative (Z)-6,4'-dihydroxy-4-methoxy-7-prenylaurone (2) were investigated. Both flavonoids, as well as cisplatin as a reference anticancer drug, were tested in vivo against ten human cancer cell lines (breast cancer (MCF-7, SK-BR-3, T47D), colon cancer (HT-29, LoVo, LoVo/Dx), prostate cancer (PC-3, Du145), lung cancer (A549) and leukemia (MV-4-11) and two normal cell lines (human lung microvascular endothelial (HLMEC)) and murine embryonic fibroblasts (BALB/3T3). Chalcone 1 and aurone 2 demonstrated potent to moderate anticancer activity against nine tested cancer cell lines (including drug-resistant ones). The antiproliferative activity of all the tested compounds against cancer and the normal cell lines was compared to determine their selectivity of action. Prenylated flavonoids, especially the semisynthetic derivative of xanthohumol (1), aurone 2, were found as selective antiproliferative agents in most of the used cancer cell lines, whereas the reference drug, cisplatin, acted non-selectively. Our findings suggest that the tested flavonoids can be considered strong potential candidates for further studies in the search for effective anticancer drugs.

Structural characteristics of a novel Bletilla striata polysaccharide and its activities for the alleviation of liver fibrosis

Liver fibrosis has proven to be the main predisposing factor for liver cirrhosis and liver cancer; however, an effective treatment remains elusive. Polysaccharides, with low toxicity and a wide range of bioactivities, are strong potential candidates for anti-hepatic fibrosis applications. For this study, a new low molecular weight neutral polysaccharide (B. striata glucomannan (BSP)) was extracted and purified from Bletilla striata. The structure of BSP was characterized and its activities for alleviating liver fibrosis in vivo were further evaluated. The results revealed that the structural unit of BSP was likely →4)-β-D-Glcp-(1 → 4)-β-D-Manp-(1 → 4)-β-D-2ace-Manp-(1 → 4)-β-D-Manp-(1 → 4)-β-D-Glcp-(1 → 4)-β-D-Manp-(1 → 4)-β-D-Manp-(1 → 4)-β-D-3ace-Manp-(1→, with a molecular weight of only 58.5 kDa. Additionally, BSP was observed to attenuate the passive impacts of liver fibrosis in a manner closely related to TLR2/TLR4-MyD88-NF-κB signaling pathway conduction. In summary, the results of this study provide theoretical foundations for the potential applications of BSP as an anti-liver fibrosis platform.

Past research and future strategies for molten chlorides application in concentrated solar power technology

This review summarizes past research and future strategies for the improvement of the pair heat transfer fluids (HTF) - containing material, used in concentrated solar power (CSP) plants, focusing on the most interesting and promising HTF, chloride molten salts. Indeed, their low cost and operating range temperature make them very strong potential candidates for future CSP plants, furthermore improvable by wisely adding nanoparticles. Nevertheless, their well-known aggressive behaviour entails selecting a long-lasting resistant alloy, which requires a better understanding of its associated corrosion mechanisms and the influences of its alloying elements. Mitigation strategy mechanisms that come from salt impurities implying purification processes are also reviewed. Finally, thermogravimetric analysis (TGA) coupled with differential scanning calorimetry (DSC) for salt preparation, and numerical simulations on Thermocalc software modelling elements activities of selected alloys and their interaction with molten chlorides are discussed.

Full-Dimensional Grain Boundary Stress Release for Flexible Perovskite Indoor Photovoltaics.

Perovskite photovoltaics are strong potential candidates to drive low-power off-grid electronics for indoor applications. Compared with rigid devices, flexible perovskite devices can provide a more suitable surface for indoor small electronic devices, enabling them have a broader indoor application prospect. However, the mechanical stability of flexible perovskite photovoltaics is an urgent issue solved. Herein, a kind of 3D crosslinking agent named borax is selected to carry out grain boundary penetration treatment on perovskite film to realize full-dimensional stress release. This strategy improves the mechanical and phase stabilities of perovskite films subjected to external forces or large temperature changes. The fabricated perovskite photovoltaics deliver a champion power conversion efficiency (PCE) of 21.63% under AM 1.5G illumination, which is the highest one to date. The merit of low trap states under weak light makes the devices present a superior indoor PCE of 31.85% under 1062 lux (LED, 2956 K), which is currently the best flexible perovskite indoor photovoltaic device. This work provides a full-dimensional grain boundary stress release strategy for highly stable flexible perovskite indoor photovoltaics.

Evaluation of anti-histidine-rich protein 2 monoclonal antibodies, developed by using poly (N-isopropylacrylamide) as an adjuvant for malarial diagnostic application

To evaluate the sensitivity and the stability of the monoclonal antibodies (Aa3c10, b10c1), against truncated Histidine-rich protein 2 (PfHRP2), developed using smart polymer, poly N-isopropylacrylamide, as adjuvant for malarial diagnostic applications in comparison with the available commercial antibodies. Two hybridoma clones (Aa3c10, b10c1) were used for the production of ascites in BALB/c mice. Purification of monoclonal antibodies from the ascites was carried out using affinity columns. The thermal stability study of monoclonal antibodies was done by storing it at 37°C and 45°C for thirty days. The stored antibodies were analyzed using SDS-PAGE and flow-through device where the antigenantibody interaction was visualized by Protein A colloidal gold solution. Sensitivity was determined by endpoint dilution ELISA and the dissociation constant by competitive ELISA. Sensitive pair optimization was done by sandwich ELISA using biotinylated antibodies. Prototype preparation for lateral flow assay had a colloidal gold-based detection system. Thermal stability experiments showed that both mAbs (Aa3c10; b10c1) are stable up to thirty days at 45°C while the commercially available mAbs were stable up to fifteen days only. Compared to commercial antibodies, the mAb Aa3c10, showed the highest sensitivity in end-point titre. In sensitive pair optimization, it was observed that the mAb, b10c1, as a detector and the mAb, Aa3c10, as a capture antibody showed the highest absorbance to detect 50pg/ml PfHRP2 antigen. The prototype formulation of lateral flow assay using the mAbs (Aa3c10; b10c1) showed good reactivity with WHO panel and no false-positive results were observed with twenty clinically negative samples and five P. vivax positive samples. The novel monoclonal antibodies (Aa3c10, b10c1) against truncated PfHRP2, could be a strong potential candidates that can be included in making RDTs with better sensitivity and stability.

Dimensionless correlations and performance maps of scroll expanders for micro-scale Organic Rankine Cycles

In the endeavor towards distributed power systems, not seasonal-dependent micro-power generation technologies are expected to integrate the energy scenario in the years to come. In this context, the Organic Rankine Cycle (ORC) in the (1–10) KWe scale has chronically lacked a suitable expansion device, hindering its market attractiveness. As scroll expanders have been pointed out as strong potential candidates, performance correlations and pre-design maps based on a review and analysis of published experimental data are presented. A dimensionless approach based on the traditional Ns, Ds dimensionless numbers stemming from turbomachinery has been chosen for greater generality. In addition, the lubricating oil mass fraction effect on the scroll expander performance has been included. The generated maps contribute to accelerating the pre-design phases at the system and component level with beneficial effects for the overall development process. Basic geometry and size characteristics are considered as well, acknowledging their importance in micro-power embedded applications; these considerations are illustrated in a passenger car waste-heat recovery case study. Findings suggest that optimized scroll expanders may potentially reach very interesting nominal electric isentropic efficiencies (up to 80% for an oil lubricated scroll expander).

Synthesis and Characterization of Metal-Encapsulating Si16 Cage Superatoms

Nanoclusters, aggregates of several to hundreds of atoms, have been one of the central issues of nanomaterials sciences owing to their unique structures and properties, which could be found neither in nanoparticles with several nanometer diameters nor in organometallic complexes. Along with the chemical nature of each element, properties of nanoclusters change dramatically with size parameters, making nanoclusters strong potential candidates for future tailor-made materials; these nanoclusters are expected to have attractive properties such as redox activity, catalysis, and magnetism. Alloying of nanoclusters additionally gives designer functionality by fine control of their electronic structures in addition to size parameters. Among binary nanoclusters, binary cage superatoms (BCSs) composed of transition metal (M) encapsulating silicon cages, M@Si16, have unique cage structures of 16 silicon atoms, which have not been found in elemental silicon nanoclusters, organosilicon compounds, and silicon based clathrates. The unique composition of these BCSs originates from the simultaneous satisfaction of geometric and electronic shell-closings in terms of cage geometry and valence electron filling, where a total of 68 valence electrons occupy the superatomic orbitals of (1S)2(1P)6(1D)10(1F)14(2S)2(1G)18(2P)6(2D)10 for M = group 4 elements in neutral ground state. The most important issue for M@Si16 BCSs is fine-tuning of their characters by replacement of the central metal atoms, M, based on one-by-one adjustment of valence electron counts in the same structure framework of Si16 cage; the replacement of M yields a series of M@Si16 BCSs, based on their superatomic characteristics. So far, despite these unique features probed in the gas-phase molecular beam and predicted by quantum chemical calculations, M@Si16 have not yet been isolated. In this Account, we have focused on recent advances in synthesis and characterizations of M@Si16 BCSs (M = Ti and Ta). A series of M@Si16 BCSs (M = groups 3 to 5)was found in gas-phase molecular beam experiments by photoelectron spectroscopy and mass spectrometry: formation of halogen-, rare-gas-, and alkali-like superatomswas identified through one-by-one tuning of number of total valence electrons. Toward future functional materials in the solid state, we have developed an intensive, size-selected nanocluster source based on high-power impulse magnetron sputtering coupled with a mass spectrometer and a soft-landing apparatus. With scanning probe microscopy and photoelectron spectroscopy, the structure of surface-immobilized BCSs has been elucidated; BCSs can be dispersed in an isolated form using C60 fullerene decoration of the substrate. The intensive nanocluster source also enables the synthesis of BCSs in the 100-mg scale by coupling with a direct liquid-embedded trapping method into organic dispersants, enabling their structure characterization as a highly symmetric "metal-encapsulating tetrahedral silicon-cage" (METS) structure with Frank-Kasper geometry.

From materials to systems: a multiscale analysis of nanomagnetic switching

With the increasing demand for low-power electronics, nanomagnetic devices have emerged as strong potential candidates to complement present day transistor technology. A variety of novel switching effects such as spin torque and giant spin Hall offer scalable ways to manipulate nano-sized magnets. However, the low intrinsic energy cost of switching spins is often compromised by the energy consumed in the overhead circuitry in creating the necessary switching fields. Scaling brings in added concerns such as the ability to distinguish states (readability) and to write information without spontaneous backflips (reliability). A viable device must ultimately navigate a complex multi-dimensional material and design space defined by volume, energy budget, speed and a target read-write-retention error. In this paper, we review the major challenges facing nanomagnetic devices and present a multi-scale computational framework to explore possible innovations at different levels (material, device, or circuit), along with a holistic understanding of their overall energy-delay-reliability tradeoff.

Abstract 1959: MTA1 promotes tumor progression and bone metastasis in prostate cancer via positive regulation of MUC1 and CTSB

Abstract About 80% of the time that prostate cancer cells metastasize, they spread to the bones. Metastasis involves activation of invasive programs through genetic and epigenetic alterations, including changes in expression of chromatin remodeler proteins. We have previously identified metastasis-associated protein 1 (MTA1), a chromatin remodeler, as a component of vicious cycle of bone metastasis and confirmed significantly higher expression of MTA1 in bone metastatic samples from patients. In an attempt to dissect molecular mechanisms of MTA1 action, we performed integrative analysis of our bone metastasis signature data along with MTA1 ChIP-Seq data, which revealed mucin 1 (MUC1) and cathepsin B (CTSB) as strong potential candidates responsible for MTA1-driven invasiveness.Here, we show that loss of function studies with MTA1 in PC3M cells exhibit reduced expression for MUC1 and CTSB. We also demonstrate that depletion of MTA1 in PC3M aggressive prostate cancer cellsdoes not affect cell proliferation but leads to decrease in colony forming ability, invasive and migratory property of these cells. When PC3M cells silenced for MTA1 and tagged with luciferase are used to generate subcutaneous or intracardiac xenografts, it leads to reduced tumor progression or decreased metastasis to bone, respectively as evident by bioluminescent measurements and histology of tumors. Ongoing experiments aim to validate the role of MUC1 and CTSB in MTA1-driven invasiveness and metastasis in prostate cancer. Citation Format: Avinash Kumar, Swati Dhar, Gisella Campanelli, Nasir A. Butt, Christian R. Gomez, Jason M. Schallheim, Anait S. Levenson. MTA1 promotes tumor progression and bone metastasis in prostate cancer via positive regulation of MUC1 and CTSB [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 1959. doi:10.1158/1538-7445.AM2017-1959

Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems

In this work, we report a targeted drug delivery system built by functionalizing graphene oxide (GO) with carboxymethyl chitosan (CMC), fluorescein isothiocyanate and lactobionic acid (LA). Analogous systems without LA were prepared as controls. Doxorubicin (DOX) was loaded onto the composites through adsorption. The release behavior from both the LA-functionalized and the LA-free material is markedly pH sensitive. The modified GOs have high biocompatibility with the liver cancer cell line SMMC-7721, but can induce cell death after 24h incubation if loaded with DOX. Tests with shorter (2h) incubation times were undertaken to investigate the selectivity of the GO composites: under these conditions, neither DOX-loaded system was found to be toxic to the non-cancerous L929 cell line, but the LA-containing composite showed the ability to selectively induce cell death in cancerous (SMMC-7721) cells while the LA-free analogue was inactive here also. These findings show that the modified GO materials are strong potential candidates for targeted anticancer drug delivery systems.

Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics.

Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP). Two synthetic 11-residue peptides (ATRA-1A and ATRA-2) containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4). We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost), making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP) (EC50 = 0.05 μg/mL). High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC) assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed synergism with LL-37, ATRA-1A, and hBD3-Pep4. In further studies, polymyxin B synergized with LL-37, ATRA-1A, and hBD3-Pep4 while Rifampicin synergized with LL-37 and mCRAMP for intracellular killing of mycobacteria residing inside macrophages. These studies provide the foundation for the potential development of synthetic cationic antimicrobial peptides with activity against mycobacteria.

Annealing effects on physical properties of doped CdTe thin films for photovoltaic applications

Polycrystalline Cadmium Telluride (CdTe) thin films were prepared on glass substrates by thermal evaporation at the chamber ambient temperature and then annealed for an hour in vacuum ~1×10−5mbar at 400°C. These annealed thin films were doped with copper (Cu) via ion exchange by immersing these films in Cu (NO3)2 solution (1g/1000ml) for 20min. Further these films were again annealed at different temperatures for better diffusion of dopant species. The physical properties of an as doped sample and samples annealed at different temperatures after doping were determined by using energy dispersive x-ray analysis (EDX), x-ray diffraction (XRD), Raman spectroscopy, transmission spectra analysis, photoconductivity response and hot probe for conductivity type. The optical band gap of these thermally evaporated Cu doped CdTe thin films was determined from the transmission spectra and was found to be in the range 1.42–1.75eV. The direct energy band gap was found annealing temperatures dependent. The absorption coefficient was >104cm−1 for incident photons having energy greater than the band gap energy. Optical density was observed also dependent on postdoping annealing temperature. All samples were found having p-type conductivity. These films are strong potential candidates for photovoltaic applications like solar cells.

Development of ultrafine multichannel microfluidic mixer for synthesis of bimetallic nanoclusters: catalytic application of highly monodisperse AuPd nanoclusters stabilized by poly(N-vinylpyrrolidone).

On account of their novel properties, bimetallic nanoparticles and nanoclusters (NCs) are strong potential candidates for optical, magnetic, and catalytic functional materials. These properties depend on the chemical composition and size (number of constituent atoms) of the NCs. Control of size, structure, and composition is particularly important for fabricating highly functional materials based on bimetallic NCs. Size- and structure-controlled synthesis of two-element alloys can reveal their intrinsic electronic synergistic effects. However, because synergistic enhancement of activity is strongly affected by composition as well as by size and structure, controlled synthesis is a challenging task, particularly in catalytic applications. To investigate catalytic synergistic effects, we have synthesized highly monodisperse, sub-2 nm, solid-solution AuPd NCs stabilized with poly(N-vinylpyrrolidone) (AuPd:PVP) using a newly developed ultrafine microfluidic mixing device with 15 μm wide multiple lamination channels. The synergistic enhancement for catalytic aerobic oxidation of benzyl alcohol exhibited a volcano-shaped trend, with a maximum at 20-65 at. % Pd. From X-ray photoelectron spectroscopic measurements, we confirmed that the enhanced activity originates from the enhanced electron density at the Au sites, donated by Pd sites.

Densification and characterization of SiO 2 -B 2 O 3 -CaO-MgO glass/Al 2 O 3 composites for LTCC application

Abstract A glass/ceramic composite using lead-free low melting glass (SiO2-B2O3-CaO-MgO glass) with Al2O3 fillers was investigated. X-ray diffraction analysis revealed that the anorthite and cordierite phase appeared in the sintered composites. The dilatometric analysis showed that the onset of shrinkage took place at ∼624 °C for all the samples and the onset temperature was independent on the content of glass. The low melting glass significantly promoted densification of the composites and lowered the sintering temperature to ∼875 °C. The addition of 50 wt% glass sintered at 875 °C showed er of 7.3, tan δ of 1.15×10−3, TEC of 5.41 ppm/°C, thermal conductivity of 3.56 W/m °C, and flexural strength of 184 MPa. The results showed that the SiO2-B2O3-CaO-MgO glass/Al2O3 composites were strong potential candidates for low temperature cofired ceramic substrate applications.

Some Unconventional Organic−Inorganic Hybrid Low-Dimensional Semiconductors and Related Light-Emitting Devices

Structural, optical, electrical, and optoelectronic properties, as well as prototype light-emitting devices, are being reported for the two-dimensional (quantum well) organic−inorganic hybrid semiconductor systems based on the organic cations CH3(CH2)7CH═CH(CH2)8NH3+ (OL) and on the inorganic networks formed out of MX42− anions, where M = Pb and X = I, Br, and Cl. These new crystalline compounds show extremely intense excitonic bands at chemically controllable positions in the ultraviolet−visible spectral region, with excitonic binding energies of more than 180 meV at room temperature. These novel properties render them as strong potential candidates in optoelectronic applications, comparable to the artificial low-dimensional systems. Prototype light-emitting devices (LED) based on the above-mentioned compounds exhibit naked eye electroluminescence, in some cases, semicontinuous operation, for the first time at room temperature. In addition, these devices operate at relatively low voltages and are readily realized. Because of the enhanced film-forming and degradation-resistant properties of the active materials, the device functionality is being exhibited for weeks. Thus, it is expected that this particular reported synthetic route of hybrid organic−inorganic semiconductors could provide cost-effective materials for novel optoelectronic devices. Moreover, the properties of some composite systems of the type (CH3NH3)n−1(OL)2PbnX3n+1 are being reported briefly.

Antimicrobial and antibiofilm activity of cathelicidins and short, synthetic peptides against Francisella

Francisella infects the lungs causing pneumonic tularemia. Focusing on the lung’s host defense, we have examined antimicrobial peptides as part of the innate immune response to Francisella infection. Interest in antimicrobial peptides, such as the cathelicidins, has grown due their potential therapeutic applications and the increasing problem of bacterial resistance to commonly used antibiotics. Only one human cathelicidin, LL-37, has been characterized. Helical cathelicidins have also been discovered in snakes including the Chinese King Cobra, Naja atra (NA-CATH). Four synthetic 11-residue peptides (ATRA-1, -2, -1A and -1P) containing variations of a repeated motif within NA-CATH were designed. We hypothesized that these smaller synthetic peptides could have excellent antimicrobial effectiveness with shorter length (and less cost), making them strong potential candidates for development into broad-spectrum antimicrobial compounds. We tested the susceptibility of F. novicida to four ATRA peptides, LL-37, and NA-CATH. Two of the ATRA peptides had high antimicrobial activity (μM), while the two proline-containing ATRA peptides had low activity. The ATRA peptides did not show significant hemolytic activity even at high peptide concentration, indicating low cytotoxicity against host cells. NA-CATH killed Francisella bacteria more quickly than LL-37. However, LL-37 was the most effective peptide against F. novicida (EC50 = 50 nM). LL-37 mRNA was induced in A549 cells by Francisella infection. We recently demonstrated that F. novicida forms in vitro biofilms. LL-37 inhibited F. novicida biofilm formation at sub-antimicrobial concentrations. Understanding the properties of these peptides, and their endogenous expression in the lung could lead to potential future therapeutic interventions for this lung infection.

The influence of an alkenyl terminal group on the mesomorphic behaviour and electro-optic properties of fluorinated terphenyl liquid crystals

Novel liquid crystal terphenyls with two, three and four lateral fluoro substituents and an alkene unit at the end of a terminal chain are presented in terms of synthesis, mesomorphic behaviour and electro-optic properties. The difluoro analogues were found to exhibit the smectic C phase over a wide temperature range, with short temperature ranges of the smectic A and the nematic phase above. Very low melting points were recorded for the trifluoro analogues, and the shorter chain homologues of these materials exhibit the nematic phase over a wide temperatures with a monotropic smectic C phase and the higher homologues exhibit the smectic C phase over a wide temperature range with the nematic phase above. The tetrafluoroterphenyls exhibit the nematic phase over a wide temperature range with the complete absence of smectic phases. As appropriate, the materials were evaluated for dielectric anisotropy and threshold voltage in nematic phase, and mixed with a chiral dopant to evaluate the spontaneous polarisation, tilt angle and switching times in the chiral smectic C phase. The results show that these compounds are strong potential candidates for application in both vertically aligned nematic (VAN) and ferroelectric liquid crystal (FLC) devices.

Quality Counts: Extending the Strategic Politician Model of Incumbent Deterrence

Competitive elections are essential to representative democracy. Competition in U.S. House elections is low in part because incumbents have strategic advantages that deter strong potential candidates from running. Many observers conclude that incumbents retain their seats without full accountability to the electorate, but the mechanisms of deterrence have never been fully explored from the perspective of strong potential candidates. Based on a survey of potential House candidates designed to capture perceptions of incumbents' personal quality and reelection prospects, we find strong evidence for the “strategic politicians” thesis (Black 1972; Jacobson and Kernell 1983). We extend the logic of the strategic model first by showing that incumbents' reelection prospects are affected by their personal quality and second by demonstrating that incumbents' personal qualities deter strong challengers from running, independent of their electoral prospects. Our findings prompt us to suggest revisions to our understanding of competition and representation in contemporary House elections.