Addressing Drug Resistance in Cancer: A Team Medicine Approach.

Drug resistance remains one of the major impediments to treating cancer. Although many patients respond well initially, resistance to therapy typically ensues. Several confounding factors appear to contribute to this challenge. Here, we first discuss some of the challenges associated with drug resistance. We then discuss how a 'Team Medicine' approach, involving an interdisciplinary team of basic scientists working together with clinicians, has uncovered new therapeutic strategies. These strategies, referred to as intermittent or 'adaptive' therapy, which are based on eco-evolutionary principles, have met with remarkable success in potentially precluding or delaying the emergence of drug resistance in several cancers. Incorporating such treatment strategies into clinical protocols could potentially enhance the precision of delivering personalized medicine to patients. Furthermore, reaching out to patients in the network of hospitals affiliated with leading academic centers could help them benefit from such innovative treatment options. Finally, lowering the dose of the drug and its frequency (because of intermittent rather than continuous therapy) can also have a significant impact on lowering the toxicity and undesirable side effects of the drugs while lowering the financial burden carried by the patient and insurance providers.

Peritumoral Immunoglobulin M Lambda Light Chain Amyloidosis in a Patient With Advanced Follicular Lymphoma.

Peritumoral light chain (AL) amyloidosis secondary to lymphoid malignancies is a rare but well-described entity. Peritumoral deposition of amyloid without systemic amyloidosis has been described in mucosa-associated lymphoid tissue (MALT) lymphomas; however, there are no reported cases of follicular lymphoma with localized peritumoral AL amyloidosis without systemic involvement of amyloidosis. We present a rare case of a patient with advanced follicular lymphoma with peritumoral lymph node IgM lambda light chain amyloidosis without an underlying monoclonal gammopathy or plasma cell dyscrasia.

Why Do Relative Intensities of Charge Transfer and Intra-4f Transitions of Eu3+ Ion Invert in Yttrium Germanate Hosts? Unravelling the Underlying Intricacies from Experimental and Theoretical Investigations.

The dominant intensity of parity-forbidden intra-4f transitions of europium(III) over O → Eu charge-transfer band (CTB) intensity is against common perceptions, yet this trend is observed in many germanate hosts and has not been rationalized so far. In search of a plausible explanation for this unusual trend, present work reports an experimental and theoretical investigations in conjunction on two sibling germanate host, namely, Y2GeO5 and Y2Ge2O7 having dopant Eu3+ in their respective YO7 polyhedra. Whereas for Y2GeO5:Eu3+, the CTB is more intense than the intra-4f transitions in the excitation spectrum, in the case of Y2Ge2O7:Eu3+, the relative intensities of CTB and intra-4f transitions are reversed. Comparative structural analysis reveals that Eu3+ present in YO7 of Y2GeO5 has a greater number of tetra-coordinated oxygen (Otetra) and yttrium atom as first and second neighbors, respectively (Eu3+-Otetra-Y3+ linkages). Conversely, in Y2Ge2O7 host, the Eu3+ ion mostly has tricoordinated oxygen (Otri) as its nearest neighbor and germanium ions next to Otri (Eu3+-Otri-Ge4+ linkage). Theoretical calculations reveal that while Y2GeO5:Eu has Otetra(4Y) dominating at the Fermi level and the 4f state of Eu3+ remains inert toward mixing, in Y2Ge2O7:Eu, the Fermi level has major contribution from Otri(2Y + 1Ge) with significant mixing with 4f states of Eu. The dominant control of Eu3+-Otri-Ge4+ linkages in geometrical and electronic structure of Y2Ge2O7:Eu owing to the GeO4 surrounding has been attributed to relative poor intensity of O → Eu CTB. Siege of Eu3+ by GeO4 and subsequent occurrence of Eu3+-Otri-Ge4+ linkages play a dual role: First, it induces electronic rigidity to hinder excitation of electron at bridging (Otri) oxygen by highly charged small Ge4+ cation; second, the covalent character in Eu-O bond is achieved by intermixing of Eu's 4f and Otri 2p orbital which facilitates relaxing of the parity-selection rule thus enhancing the probability of intra-4f transitions. The inferences drawn remain valid when extrapolated to other inorganic oxides having EuOx polyhedra surrounded by covalent units like PO4, SiO4, etc. and have a prevailing number of low-coordinated oxygen atoms and highly charged small cation in the first and second coordination shells, respectively. The optical basicity concept is also found to endorse our explanation. These remarkable generic inferences will pave the rational way for designing efficient phosphors for solid-state lighting.

Effect of Bi3+ addition on the upconversion luminescence properties of NaYbF4 :Er.

In this study, Bi3+ incorporation in NaYbF4 :Er lattice and its influence on upconversion luminescence properties have been investigated in detail using techniques such as temperature-dependent luminescence, Fourier transform infrared spectroscopy and X-ray diffraction (XRD). The study was carried out to develop phosphors with improved upconversion luminescence. From photoluminescence and lifetime measurements it is inferred that luminescence intensity from NaYbF4 :Er increases with Bi3+ addition. The sample containing 50 at.% Bi3+ ions exhibited optimum upconversion luminescence. Increased distance between Yb3+ -Yb3+ and Er3+ -Er3+ due to Bi3+ incorporation into the lattice and associated decrease in the extent of dipolar interaction/self-quenching are responsible for increase in lifetime values and luminescence intensities from Er3+ ions. Incorporation of Bi3+ into NaYbF4 :Er lattice reduced self-quenching among Yb3+ -Yb3+ ions and this facilitated energy transfer from Yb3+ to Er3+ . This situation also explains decrease in the extent of temperature-assisted quenching of emission from thermally coupled 2 H11/2 and 4 S3/2 levels of Er3+ . Based on Rietveld refinement of XRD patterns it was confirmed that a maximum of 10 at.% of Bi3+ added was incorporated into the NaYbF4 :Er lattice and the remaining complex co-exists as a BiOF phase. These results are of significant interest in the area of development of phosphors based on Yb3+ -Er3+ upconversion luminescence.

Improving green emission of Tb3+ ions in BaO-B2 O3 -P2 O5 glasses by means of Al3+ ions.

BaO-B2 O3 -P2 O5 glasses doped with a fixed concentration of Tb3+ ions and varying concentrations of Al2 O3 were synthesized, and the influence of the Al3+ ion concentration on the luminescence efficiency of the green emission of Tb3+ ions was investigated. The optical absorption, excitation, luminescence spectra and fluorescence decay curves of these glasses were recorded at ambient temperature. The emission spectra of terbium ions when excited at 393 nm exhibited two main groups of bands, corresponding to 5 D3  â†’ 7 Fj (blue region) and 5 D4  â†’ 7Fj (green region). From these spectra, the radiative parameters, viz., spontaneous emission probability A, total emission probability AT , radiative lifetime τ and fluorescent branching ratio ß, of different transitions originating from the 5 D4 level of Tb3+ ions were evaluated based on the Judd-Ofelt theory. A clear increase in the quantum efficiency and luminescence of the green emission of Tb3+ ions corresponding to 5 D4  â†’ 7 F5 transition is observed with increases in the concentration of Al2 O3 up to 3.0 mol%. The improvement in emission is attributed to the de-clustering of terbium ions by Al3+ ions and also to the possible admixing of wave functions of opposite parities. Copyright © 2016 John Wiley & Sons, Ltd.

Bifunctional Li and Co Doped ZnO Nanostructures Synthesized by Solvothermal Method: Stabilizer Controlled Shape and Size Tuning.

1D nanostructures of ZnO, Zn0.95Co0.05O and Zn0.85Co0.05Li0.10 were synthesized by a solvothermal chemical method with and without using oleic acid as a stabilizer. We report a very interesting observation of both room temperature ferromagnetism and photoluminescence properties along with development of different morphological transformation of these nanostructures on doping Co and Li in ZnO in the presence and absence of oleic acid. Zn0.95Co0.05O sample prepared in the presence of oleic acid showed increased saturation magnetization value (~ 4.1 emu/g and) compared to Zn0.95Co0.05O prepared without oleic acid (~ 1.1 emu/g). In both the cases it is observed that Li incorporation further enhances the room temperature ferromagnetic (RTFM) behavior and saturation magnetization values (~ 6 emu/g) of luminescent Zn0.95Co0.05 nanostructures. These results are significant, as the luminescent 1 D RTFM materials will have implications in photo magnetic devices like magneto-optical switches and sensors.

The dual role of palladium in enhancing the photocatalytic activity of CdS dispersed on NaY-zeolite.

A stable photocatalyst, CdS dispersed on zeolite with Pd as both the dopant and the co-catalyst, has been developed. Enhancement of photocatalytic activity for hydrogen generation is observed for CdS when doped with palladium and dispersed on NaY-zeolite (CdPdS-Z). A further increase in the photocatalytic activity of CdPdS-Z is observed when palladium is added as a co-catalyst (Pd-CdPdS-Z). Cd0.95Pd0.05S-Z is synthesized via a facile soft chemical route and the Pd co-catalyst is loaded onto the composite using a wet impregnation method. This composite catalyst exists as two phases consisting of CdPdS and zeolite and CdPdS exists as a highly dispersed phase on zeolite as revealed by TEM studies. The Pd doped CdS-zeolite composite exhibits increased visible light absorption indicating the alteration of the band structure of CdS as a result of doping. Time resolved fluorescence studies reveal that the lifetime of the charge carriers is higher in the composites than in pure CdS. A detailed characterization using XRD, Raman and X-ray photoelectron spectroscopy indicates that Pd has substituted for Cd in the CdS lattice and Pd exists in the Pd(2+) oxidation state. Solid state MAS NMR studies indicate that an interaction exists between CdS (or CdPdS) and zeolite at the interface and Cd selectively interacts with Al of the zeolite framework. The photocatalytic activity of the Pd-CdPdS-Z catalyst remains unchanged with repeated cycles. Characterization of the used catalyst indicates that it is stable under the present experimental conditions. The enhanced photocatalytic activity of Pd-CdPdS-Z is attributed to the enhanced visible light absorption arising due to Pd doping and increased lifetime of the photogenerated charge carriers assisted by zeolite and the Pd co-catalyst. This study highlights the multiple roles played by palladium in enhancing the photocatalytic activity of the CdS-zeolite composite.

Disordered self assembled monolayer dielectric induced hysteresis in organic field effect transistors.

A memory device using an organic field effect transistor (OFET) with copper phthalocyanine (CuPc) as active material was fabricated and studied. For this purpose, SiO2 dielectric surface was modified with a disordered self assembled monolayer (SAM) of octadecyltrichlorosilane (OTS) molecule which was found to induce large disorder in CuPc film thereby generating more traps for charge carriers. Drain current-drain voltage characteristics at zero gate voltage exhibited large hysteresis which was not observed in OFET devices with ordered OTS monolayer modified and unmodified SiO2 dielectrics. The extent of hysteresis and drain current on/off ratio, reading voltage etc. were found to be dependent on the sweep rate/step voltage employed during scanning. Highest hysteresis with on/off ratio of about 240 was obtained for an optimum step voltage of 2 V while it decreased with further reduction in the same. This was attributed to the longer scanning time leading to release of trapped carriers during forward scan itself. The OFET device was found to exhibit excellent memory retention capability where OFF and ON current measured for about 2 hours after stressing the device at write and erase voltages showed good retention of on/off ratio.

Structural, luminescence and EPR studies on SrSnO3 nanorods doped with europium ions.

The present study describes the structural and luminescent properties of SrSnO(3) nanorods containing Eu(3+) ions. Based on Rietveld refinement of XRD patterns corresponding to both undoped and europium doped SrSnO(3) nanorods, it is inferred that the average bond lengths of Sr-O1 linkages, which have a square planar geometry around Sr(2+) in the SrO(12) polyhedra present in SrSnO(3), remained unaffected with Eu(3+) incorporation into the lattice. However, the average bond lengths of shorter Sr-O2 linkages increase and longer Sr-O2 linkages decrease with Eu(3+) doping into the SrSnO(3) lattice. A lack of variation in the lattice parameters of SrSnO(3) with doped Eu(3+) ions is explained based on mutually compensating changes in the average bond lengths of the Sr-O2 linkages in the unit cell. Luminescence studies have confirmed that Eu(3+) ions occupy the centrosymmetric Sr(2+) site only up to 2 at%, beyond which Eu(3+) ions exist in a significantly distorted environment (grain boundaries). Beyond 3%, incorporation of Eu(3+) ions into the SrSnO(3) lattice leads to the formation of a Eu(2)Sn(2)O(7) phase. From the EPR studies it is confirmed that around 5% of the incorporated Eu(3+) ions get converted to Eu(2+) ions and they occupy Sr(2+) sites in the lattice.

Evaluation of interparticle interaction between colloidal Ag nanoparticles coated with trisodium citrate and safranine by using FRET: spectroscopic and mechanistic approach.

Current study employs fluorescence spectroscopy, UV-Vis absorbance spectroscopy, dynamic light scattering (DLS) and cyclic voltammetry (CV) to investigate the interaction of safranine dye with spherical shaped silver nanoparticles (AgNPs) coated with trisodium citrate. In fluorescence spectroscopic study we used the AgNPs and safranine dye as component molecules for the construction of FRET, whereas AgNPs serve as donor fluorophore and safranine as acceptor. The fluorescence quenching of AgNPs followed by sensitization of safranine occurs almost simultaneously by addition of safranine dye with different concentrations, indicating fluorescence energy transfer observed between them. Interaction between safranine and AgNPs is also confirmed by using UV-Vis absorption spectroscopy. Addition of safranine results in the significant decrease in the absorbance of AgNPs at 423 nm and simultaneous increase in the absorbance of safranine at 518, 276 and 248 nm which is indication of rapid binding of safranine molecules with AgNPs. However CV measurements reveals that the safranine molecule does not alter the redox properties of the AgNPs but the safranine molecule lose their redox properties upon getting bonded with AgNPs. This clearly confirms that the safranine molecules get attached on the surface of AgNPs which was also supported by the DLS as well as zeta potential measurement.

Differential distribution of pigment-protein complexes in the Thylakoid membranes of Synechocystis 6803.

Thylakoids in Synechocystis 6803, though apparently uniform in appearance in ultrastructure, were found to consist of segments which were functionally dissimilar and had distinct proteomes. These thylakoid segments can be isolated from Synechocystis 6803 by successive ultracentrifugation of cell free extracts at 40,000×g (40 k segments), 90,000×g (90 k segments) and 150,000×g (150 k segments). Electron microscopy showed differences in their appearance. 40 k segments looked feathery and fluffy, whereas the 90 k and 150 k thylakoid membrane segments appeared tiny and less fluffy. The absorption spectra showed heterogeneous distribution of pigment-protein complexes in the three types of segments. The photochemical activities of Photosystem I (PSI) and Photosystem II (PSII) showed unequal distributions in 40 k, 90 k and 150 k segments which were substantiated with low temperature fluorescence measurements. The ratio of PSII/PSI fluorescence emission at 77 K (λ(ex) = 435 nm) was highest in 150 k segments indicating higher PSII per unit PSI in these segments. The chlorophyll fluorescence lifetimes in the membranes, determined with a time-correlated single-photon counting technique, could be resolved in three components: τ(1) (=) <40 ps, τ(2) (=) 425-900 ps and τ(3) (=) 2.4-3.2 ns. The percentage contribution of the fastest component (τ(1)) decreased in the order 40 k > 90 k > 150 k segments whereas that of the other two components showed a reversed trend. These studies indicated differential distribution of pigment-protein complexes in the three membrane segments suggesting heterogeneity in the thylakoids of Synechocystis 6803.

Multicolored and white-light phosphors based on doped GdF3 nanoparticles and their potential bio-applications.

Rare-earth-doped gadolinium fluoride nanocrystals were synthesized by a single step synthesis employing ethylene glycol as solvent. Based on X-ray diffraction studies, stabilization of hexagonal modification of GdF(3) has been inferred. The microscopic studies show formation of uniformly distributed nanocrystals (~15 nm). The nanoparticles are readily dispersible in water and show bright luminescence in colloidal solution. The luminescence properties have been investigated as a function of activator concentrations, and enhanced optical properties have been attributed to efficient energy transfer from the Gd(3+) to the activator RE(3+) ions, which has further been confirmed by steady-state and time-resolved optical studies. It has been demonstrated that on doping appropriate amount of activators in host GdF(3), a novel white-light-emitting phosphor is obtained with CIE co-ordinates and correlated color temperature (CCT) very close to broad daylight. This can have promising applications as phosphor for white-light ultraviolet-light-emitting diodes (UV-LEDs). Our experiments showed efficient labeling of human breast carcinoma cells (MCF-7) by Tb(3+)-doped GdF(3) nanoparticles. The fluorescence intensity was found to be dependent on the surface modifying/coating agent, and the results were validated using confocal microscopy in terms of localization of these functionalized nanoparticles.

Boroaluminosilicate glasses: novel sorbents for separation of Th and U.

Boroaluminosilicate glass having a specific composition could be successfully used for the selective uptake of thorium from a mixture containing uranium by controlling the solution pH only. Single ion uptake studies showed that the uptake of uranium and thorium was maximum at pH of 4.5 and 7.5, respectively. But uptake studies using mixtures with uranium and thorium showed that irrespective of the pH, the uptake of thorium was higher than that of uranium.

Surface functionalized silver nanoparticle conjugates: demonstration of uptake and release of a phototherapeutic porphyrin dye.

A facile supramolecular approach to prepare surface functionalized silver nanoparticle conjugates has been established and their enhanced molecular recognition features have been explored to demonstrate the uptake and stimulus responsive release of a phototherapeutic porphyrin dye, the TMPyP.

Solid state white light emitting systems based on CeF3: RE3+ nanoparticles and their composites with polymers.

A series of doped CeF(3): RE(3+) (RE(3+): Tb(3+), Eu(3+) and Dy(3+)) nanoparticles were synthesized, with the aim of obtaining a white light emitting composition, by a simple polyol route at 160°C and characterized by X-ray diffraction (XRD), high resolution transmission electron microscopy (HR-TEM), Fourier transform infrared spectroscopy (FT-IR) and photoluminescence. Uniformly distributed and highly water-dispersible rectangular nanoparticles (length ~15-20 nm, breadth ~5-10 nm) were obtained. The steady state and time resolved luminescence studies confirmed efficient energy transfer from the host to activator ions. Lifetime studies revealed that optimum luminescence is observed for 2.5 mol% Dy(3+) and 7.5 mol% Tb(3+). The energy transfer efficiencies (Ce(3+) to activators) were found to be 89% for CeF(3): Tb(3+) (7.5 mol%) nanoparticles and 60% for CeF(3): Dy(3+) (2.5 mol%) nanoparticles. Different concentrations of Tb(3+), Eu(3+) and Dy(3+) were doped to achieve a white light emitting phosphor for UV-based LEDs (light emitting diodes). Finally CeF(3), triply doped with 2.0 mol%Tb(3+), 4.5 mol% Eu(3+) and 3.5 mol% Dy(3+), was found to have impressive chromaticity co-ordinates, close to broad day light. The colloidal solutions of doped CeF(3) nanoparticles emitted bright green (Tb(3+)), blue (Dy(3+)) and white (triply doped) luminescence upon host excitation. Composites of poly methyl methacrylate (PMMA) and poly vinyl alcohol (PVA) were made with CeF(3): 5.0 mol%Tb(3+), CeF(3): 5.0 mol% Dy(3+) and triply doped white light emitting composition. The CeF(3)/PMMA (PVA) nanocomposite films, so obtained, are highly transparent (in the visible spectral range) and exhibit strong photoluminescence upon UV excitation.

Barium borosilicate glass as a matrix for the uptake of dyes.

Barium borosilicate (BBS) and sodium borosilicate (SBS) glass samples, prepared by the conventional melt-quench method, were used for the uptake of Rhodamine 6G dye from aqueous solution. The experimental conditions were optimized to get maximum uptake and was found to be 0.4 mg of dye per gram of BBS glass sample. For the same network former to modifier ratio, barium borosilicate glasses are found to have improved extent of uptake for the dye molecules from aqueous solutions compared to sodium borosilicate glasses. Based on 29Si MAS NMR studies on these glasses, it is inferred that significantly higher number of non-bridging oxygen atoms present in barium borosilicate glasses compared to sodium borosilicate glasses is responsible for its improved uptake of Rhodamine 6G dye. 11B MAS NMR studies have confirmed the simultaneous existence of boron in BO3 and BO4 configurations in both barium borosilicate and sodium borosilicate glasses. The luminescence studies have established that the dye molecule is incorporated into the glass matrix through ion exchange mechanism by replacing the exchangeable ions like Na+/Ba2+ attached with the non-bridging oxygen atoms present in the glass.

Raman spectroscopic investigations of nanoparticles of Sn(x)Ti(1-x)O2 solid solution.

SnO2 nanoparticles dispersed in TiO2 matrix are prepared at a relatively low temperature of approximately 185 degrees C. Nanoparticles of Sn(x)Ti(1-x)O2 solid solution without significant aggregation have been prepared by annealing them at approximately 500 and 900 degrees C. X-ray diffraction and high-resolution transmission electron microscopy studies have clearly established the nano-size nature of the samples. Raman spectroscopic investigations of these samples show mixed vibrational modes, some of them being similar to TiO2 (A(1g), E(g)), while some of them are similar to SnO2 (B(2g)). The E(g) mode shows significant red shift and B(2g) mode shows significant blue shift. Unlike this A(1g) mode remains unaffected. These results are explained based on the combined effects of random alloy formation and the nano-size nature of samples.

Luminescence properties of SnO2 nanoparticles dispersed in Eu3+ doped SiO2 matrix.

SnO2 nanoparticles dispersed in Eu3+ doped silica (SnO2-SiO2:Eu3+) were prepared at a low temperature (185 degrees C) in ethylene glycol medium. Transmission electron microscopy studies on as-prepared samples have established that SnO2 nanoparticles having size of 4.6 nm are uniformly covered by the SiO2 matrix. Significant extent of exciton mediated energy transfer between SnO2 and Eu3+ ions in heat treated SnO2-SiO2:Eu3+ samples has been attributed to the diffusion of Eu3+ ions from the SiO2 matrix to the near vicinity of SnO2 nanoparticles and its incorporation in the SnO2 matrix. On the other hand, very weak energy transfer exists for SnO2:Eu3+ nanoparticles heated at different temperatures due to the phase segregation of Eu3+ ions from the matrix.

Borosilicate glasses modified with organic ligands: a new selective approach for the removal of uranyl ion.

Barium borosilicate glass was found to have high uptake capacity for many cations. To improve its selectivity, surface modification was carried out. In order to make the glass selective towards uranyl ion, organic ligands like tri-n-octylphosphine oxide (TOPO) and 8-hydroxy quinoline (Oxine) were used. It was observed that the surface modification resulted in the change in uptake property of the glass. The uptake process was faster and within 5 h, 90% of the uranyl ion could be taken up from a 0.01 mM solution. With use of the modified barium borosilicate glass and EDTA as masking agent, uranyl ion could be selectively removed from mixtures of cations.

Luminescence study on Eu(3+) doped Y(2)O(3) nanoparticles: particle size, concentration and core-shell formation effects.

Nanoparticles of Eu(3+) doped Y(2)O(3) (core) and Eu(3+) doped Y(2)O(3) covered with Y(2)O(3) shell (core-shell) are prepared by urea hydrolysis for 3 h in ethylene glycol medium at a relatively low temperature of 140 °C, followed by heating at 500 and 900 °C. Particle sizes determined from x-ray diffraction and transmission electron microscopic studies are 11 and 18 nm for 500 and 900 °C heated samples respectively. Based on the luminescence studies of 500 and 900 °C heated samples, it is confirmed that there is no particle size effect on the peak positions of Eu(3+) emission, and optimum luminescence intensity is observed from the nanoparticles with a Eu(3+) concentration of 4-5 at.%. A luminescence study establishes that the Eu(3+) environment in amorphous Y (OH)(3) is different from that in crystalline Y(2)O(3). For a fixed concentration of Eu(3+) doping, there is a reduction in Eu(3+) emission intensity for core-shell nanoparticles compared to that of core nanoparticles, and this has been attributed to the concentration dilution effect. Energy transfer from the host to Eu(3+) increases with increase of crystallinity.