Bacteria in cancer therapy: a novel experimental strategy

Resistance to conventional anticancer therapies in patients with advanced solid tumors has prompted the need of alternative cancer therapies. Moreover, the success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity to normal tissues. Several decades after Coley's work a variety of natural and genetically modified non-pathogenic bacterial species are being explored as potential antitumor agents, either to provide direct tumoricidal effects or to deliver tumoricidal molecules. Live, attenuated or genetically modified non-pathogenic bacterial species are capable of multiplying selectively in tumors and inhibiting their growth. Due to their selectivity for tumor tissues, these bacteria and their spores also serve as ideal vectors for delivering therapeutic proteins to tumors. Bacterial toxins too have emerged as promising cancer treatment strategy. The most potential and promising strategy is bacteria based gene-directed enzyme prodrug therapy. Although it has shown successful results in vivo yet further investigation about the targeting mechanisms of the bacteria are required to make it a complete therapeutic approach in cancer treatment

Phenolic and antioxidant capacity retention of potato peel waste as a function of cultivar, pretreatment and drying procedure

Drying procedures employed for potato peels (both raw and boiled) may adversely affect the useful bioactivecomponents present in them. This study envisaged the identification of a feasible drying procedure for handlingbulk potato peel waste for maximising the retention of phytochemicals in the peel powder. The total phenols (TP), flavonoids (TF) and antioxidant capacity (TAC) were assessed in peels of three commercial and one newly developed anthocyanin rich Indian potato cultivars in response to boiling pretreatment and varying drying procedures. Microwave drying (600W) was best in terms of drying rate for both raw and boiled peels. It yielded the greatest amount of TP and TF in the dried raw peel, irrespective of cultivar. Dried raw peels of an thocyanin rich Kufri Neelkanth cultivar exhibited maximum TAC. Retention of TF, metal scavenging activity and reducing power followed almost a similar pattern as TP irrespective of cultivar, pretreatment and drying procedure. Our study shows that potato peel from Kufri Neelkanth (raw) and Kufri Frysona (both raw and boiled) are best source of phenolics and flavonoids and can serve as a suitable matrix for extraction of bioactive compounds which holds promise for use in the food industry

COMPARISON OF RP-HPLC AND UV SPECTROPHOTOMETRIC METHODS FOR ESTIMATION OF HALOPERIDOL IN PURE AND PHARMACEUTICAL FORMULATION

An accurate, precise, sensitive and reproducible High-performance liquid chromatographic (HPLC) and UV spectrophotometric methods were developed and validated for the quantitative determination of haloperidol (HPD) in bulk drug and pharmaceutical formulation. Different analytical performance parameters such as linearity, precision, accuracy, specificity, limit of detection (LOD) and limit of quantification (LOQ) were determined according to International Conference on Harmonization ICH Q2B guidelines. The RP-HPLC method was developed by the isocratic technique on a reversed-phase Thermo C18 (250 × 4.6 mm, 5µm) column with mobile phase consisting of Methanol: Acetonitrile (50:50v/v) at flow rate of 1.0 ml/min. The retention time for HPD was 2.238±0.3min. The UV spectrophotometric determinations were performed at 244 nm using 80% methanol as a solvent. The linearity range for HPD was 5-25 μg/ml for both HPLC and UV method. The linearity of the calibration curves for each analyte in the desired concentration range was good (r2 >0.999) by both the HPLC and UV methods. The method showed good reproducibility and recovery with percent relative standard deviation less than 2%. Moreover, the accuracy and precision obtained with HPLC co-related well with the UV method which implied that UV spectroscopy can be a cheap, reliable and less time consuming alternative for chromatographic analysis. The proposed methods are highly sensitive, precise and accurate and hence successfully applied for determining the assay and in vitro dissolution of a marketed formulation. Keywords: HPLC, UV Spectrophotometry, Haloperidol, Pharmaceutical formulation, Method validation, Quantitative analysi

Scalar-field Pressure in Induced Gravity with Higgs Potential and Dark Matter

A model of induced gravity with a Higgs potential is investigated in detail in view of the pressure components related to the scalar-field excitations. The physical consequences emerging as an artifact due to the presence of these pressure terms are analysed in terms of the constraints parting from energy density, solar-relativistic effects and galactic dynamics along with the dark matter halos.Comment: 26 pages, 3 figures, Minor revision, Published in JHE

Gravitational collapse with tachyon field and barotropic fluid

A particular class of space-time, with a tachyon field, \phi, and a barotropic fluid constituting the matter content, is considered herein as a model for gravitational collapse. For simplicity, the tachyon potential is assumed to be of inverse square form i.e., V(\phi) \sim \phi^{-2}. Our purpose, by making use of the specific kinematical features of the tachyon, which are rather different from a standard scalar field, is to establish the several types of asymptotic behavior that our matter content induces. Employing a dynamical system analysis, complemented by a thorough numerical study, we find classical solutions corresponding to a naked singularity or a black hole formation. In particular, there is a subset where the fluid and tachyon participate in an interesting tracking behaviour, depending sensitively on the initial conditions for the energy densities of the tachyon field and barotropic fluid. Two other classes of solutions are present, corresponding respectively, to either a tachyon or a barotropic fluid regime. Which of these emerges as dominant, will depend on the choice of the barotropic parameter, \gamma. Furthermore, these collapsing scenarios both have as final state the formation of a black hole.Comment: 18 pages, 7 figures. v3: minor changes. Final version to appear in GR

Pressure dependent electronic properties of MgO polymorphs: A first-principles study of Compton profiles and autocorrelation functions

The first-principles periodic linear combination of atomic orbitals method within the framework of density functional theory implemented in the CRYSTAL06 code has been applied to explore effect of pressure on the Compton profiles and autocorrelation functions of MgO. Calculations are performed for the B1, B2, B3, B4, B8_1 and h-MgO polymorphs of MgO to compute lattice constants and bulk moduli. The isothermal enthalpy calculations predict that B4 to B8_1, h-MgO to B8_1, B3 to B2, B4 to B2 and h-MgO to B2 transitions take place at 2, 9, 37, 42 and 64 GPa respectively. The high pressure transitions B8_1 to B2 and B1 to B2 are found to occur at 340 and 410 GPa respectively. The pressure dependent changes are observed largely in the valence electrons Compton profiles whereas core profiles are almost independent of the pressure in all MgO polymorphs. Increase in pressure results in broadening of the valence Compton profiles. The principal maxima in the second derivative of Compton profiles shifts towards high momentum side in all structures. Reorganization of momentum density in the B1 to B2 structural phase transition is seen in the first and second derivatives before and after the transition pressure. Features of the autocorrelation functions shift towards lower r side with increment in pressure.Comment: 19 pages, 8 figures, accepted for publication in Journal of Materials Scienc

General Minimal Flavor Violation

A model independent study of the minimal flavor violation (MFV) framework is presented, where the only sources of flavor breaking at low energy are the up and down Yukawa matrices. Two limits are identified for the Yukawa coupling expansion: linear MFV, where it is truncated at the leading terms, and nonlinear MFV, where such a truncation is not possible due to large third generation Yukawa couplings. These are then resummed to all orders using non-linear sigma-model techniques familiar from models of collective breaking. Generically, flavor diagonal CP violating (CPV) sources in the UV can induce O(1) CPV in processes involving third generation quarks. Due to a residual U(2) symmetry, the extra CPV in B_d-\bar B_d mixing is bounded by CPV in B_s-\bar B_s mixing. If operators with right-handed light quarks are subdominant, the extra CPV is equal in the two systems, and is negligible in processes involving only the first two generations. We find large enhancements in the up type sector, both in CPV in D-\bar D mixing and in top flavor violation.Comment: 5 pages and no figure

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Sulfur Nanoparticles Synthesis and Characterization from H2S Gas, Using Novel Biodegradable Iron Chelates in W/O Microemulsion

Sulfur nanoparticles were synthesized from hazardous H2S gas using novel biodegradable iron chelates in w/o microemulsion system. Fe3+–malic acid chelate (0.05 M aqueous solution) was studied in w/o microemulsion containing cyclohexane, Triton X-100 andn-hexanol as oil phase, surfactant, co-surfactant, respectively, for catalytic oxidation of H2S gas at ambient conditions of temperature, pressure, and neutral pH. The structural features of sulfur nanoparticles have been characterized by X-ray diffraction (XRD), transmission electron microscope (TEM), energy dispersive spectroscopy (EDS), diffused reflectance infra-red Fourier transform technique, and BET surface area measurements. XRD analysis indicates the presence of α-sulfur. TEM analysis shows that the morphology of sulfur nanoparticles synthesized in w/o microemulsion system is nearly uniform in size (average particle size 10 nm) and narrow particle size distribution (in range of 5–15 nm) as compared to that in aqueous surfactant systems. The EDS analysis indicated high purity of sulfur (>99%). Moreover, sulfur nanoparticles synthesized in w/o microemulsion system exhibit higher antimicrobial activity (against bacteria, yeast, and fungi) than that of colloidal sulfur