Synthesis of boron doped C3N4/NiFe2O4 nanocomposite: An enhanced visible light photocatalyst for the degradation of methylene blue

In this paper, we report the synthesis of boron doped C3N4/NiFe2O4 nanocomposite and its application as a visible-light photocatalyst for the degradation of methylene blue (MB). Boron-doped C3N4 (BCN) was prepared by simple thermal condensation of dicyandiamide with boric acid, and NiFe2O4 nanoparticles were prepared by the simple sol-gel method. The as-synthesized nanocomposite materials were characterized and confirmed by the X-ray diffraction spectroscopy, Fourier-transform infrared spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, UV-Visible diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy, and photoluminescence spectroscopy. The photocatalytic activity of BCN/NiFe2O4 nanocomposite was evaluated towards the degradation of MB in the presence of visible light irradiation. The obtained results confirmed that BCN/NiFe2O4 composite has higher degradation efficiency (98%) than that of BCN and NiFe2O4

Novel electrochemical synthesis of cellulose microfiber entrapped reduced graphene oxide: A sensitive electrochemical assay for detection of fenitrothion organophosphorus pesticide

Over the past decades, the synthesis of carbohydrate polymers incorporated graphene or reduced graphene oxide has received greater attention in different disciplines owing to their unique physicochemical properties. In this context, we report a facile electrochemical synthesis of cellulose microfibers supported reduced graphene oxide and its application towards enhanced and lower potential electrochemical detection of fenitrothion. The synthesized cellulose microfibers supported reduced graphene oxide composite was further characterized using Fourier-transform infrared spectroscopy, Raman spectroscopy and high resolution scanning electron microscopy. Cyclic voltammetry studies reveal that cellulose microfibers supported reduced graphene oxide composite modified screen-printed carbon electrode exhibits a superior electro-reduction ability and lower reduction potential towards fenitrothion compared to screen-printed carbon electrodes modified with graphene oxide, graphene oxide-cellulose microfibers, and reduced graphene oxide. Furthermore, cellulose microfibers supported reduced graphene oxide composite modified electrode showed 141 mV lower reduction potential towards fenitrothion than the chemically reduced graphene oxide- cellulose microfibers composite modified screen-printed carbon electrode. The effect of accumulation time, catalyst loading, scan rate and pH for the detection of fenitrothion has been studied and discussed. Differential pulse voltammetric studies show that the fabricated composite electrode can detect the fenitrothion in a wider linear response range up to 1.134 mM with a detection limit of 8 nM. To validate the proof of concept, the fabricated sensor was successfully applied for the detection of fenitrothion in different water samples

Facile synthesis of cellulose microfibers supported palladium nanospindles on graphene oxide for selective detection of dopamine in pharmaceutical and biological samples

The cost-effective synthesis of novel functional nanomaterials has received significant attention in the physical and chemical sciences due to their improved surface area, high catalytic activity along with unique morphological features. This paper reports a facile and eco-friendly synthesis of spindle-like palladium nanostructures (PdSPs) on graphene oxide-cellulose microfiber (GO-CMF) composite for the first time. The GO-CMF/PdSPs composite was synthesized by an electrochemical method without the use of additional surfactants and capping agents. The synthesized materials were characterized and confirmed by using transmission electron microscopy, high-resolution scanning electron microscopy, X-ray diffraction spectroscopy, Raman spectroscopy and Fourier-transform infrared spectroscopy. As-synthesized GO-CMF/PdSPs composite modified electrode was used as a selective electrocatalyst for the oxidation of dopamine (DA). The electrochemical redox behaviors of DA were investigated using cyclic voltammetry (CV). The CV results revealed that the GO-CMF/PdSPs composite modified electrode has 10 folds enhanced oxidation current response to DA than GO, PdSPs and GO-CMF modified GCEs. Under optimized conditions, the GO-CMF/PdSPs composite sensor exhibits a linear response to DA in the concentration range from 0.3 to 196.3 μM with the lower detection limit of 23 nM. The nanocomposite electrode also shows promising features towards the reliable and selective detection of DA, which includes high stability, reproducibility and high selectivity towards the commonly interfering species such as ascorbic acid, uric acid, and dihydroxybenzene isomers. The sensor was successfully tested for the real-time detection of DA in the commercial DA injections and human serum samples

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Glucocorticoid-Treated Mice Are an Inappropriate Positive Control for Long-Term Preclinical Studies in the mdx Mouse

Dmd(mdx) (mdx) mice are used as a genetic and biochemical model of dystrophin deficiency. The long-term consequences of glucocorticoid (GC) treatment on dystrophin-deficient skeletal and heart muscle are not yet known. Here we used systematic phenotyping to assess the long-term consequences of GC treatment in mdx mice. Our investigation addressed not only the effects of GC on the disease phenotype but also the question of whether GCs can be used as a positive control for preclinical drug evaluations.We performed nine pre-clinical efficacy trials (treated N = 129, untreated N = 106) of different durations in 9-to-50-week-old dystrophic mdx mice over a 3-year time period using standardized methods. In all these trials, we used either 1 mg/kg body weight of prednisone or 5 mg/kg body weight of prednisolone as positive controls to compare the efficacy of various test drugs. Data from untreated controls and GC-treated mice in the various trials have been pooled and analyzed to assess the effects of GCs on dystrophin-deficient skeletal and cardiac muscles of mdx mice. Our results indicate that continuous GC treatment results in early (e.g., at 50 days) improvements in normalized parameters such as grip strength, motor coordination and maximal in vitro force contractions on isolated EDL muscle, but these initial benefits are followed by a progressive loss of muscle strength after 100 days. We also found a significant increase in heart fibrosis that is reflected in a significant deterioration in cardiac systolic function after 100 days of treatment.Continuous administration of prednisone to mdx mice initially improves skeletal muscle strength, but further therapy result in deterioration of muscle strength and cardiac function associated with enhanced cardiac fibrosis. These results suggest that GCs may not serve as an appropriate positive control for long-term mdx mouse preclinical trials

Evolutionary Patterning: A Novel Approach to the Identification of Potential Drug Target Sites in Plasmodium falciparum

Malaria continues to be the most lethal protozoan disease of humans. Drug development programs exhibit a high attrition rate and parasite resistance to chemotherapeutic drugs exacerbates the problem. Strategies that limit the development of resistance and minimize host side-effects are therefore of major importance. In this study, a novel approach, termed evolutionary patterning (EP), was used to identify suitable drug target sites that would minimize the emergence of parasite resistance. EP uses the ratio of non-synonymous to synonymous substitutions (ω) to assess the patterns of evolutionary change at individual codons in a gene and to identify codons under the most intense purifying selection (ω≤0.1). The extreme evolutionary pressure to maintain these residues implies that resistance mutations are highly unlikely to develop, which makes them attractive chemotherapeutic targets. Method validation included a demonstration that none of the residues providing pyrimethamine resistance in the Plasmodium falciparum dihydrofolate reductase enzyme were under extreme purifying selection. To illustrate the EP approach, the putative P. falciparum glycerol kinase (PfGK) was used as an example. The gene was cloned and the recombinant protein was active in vitro, verifying the database annotation. Parasite and human GK gene sequences were analyzed separately as part of protozoan and metazoan clades, respectively, and key differences in the evolutionary patterns of the two molecules were identified. Potential drug target sites containing residues under extreme evolutionary constraints were selected. Structural modeling was used to evaluate the functional importance and drug accessibility of these sites, which narrowed down the number of candidates. The strategy of evolutionary patterning and refinement with structural modeling addresses the problem of targeting sites to minimize the development of drug resistance. This represents a significant advance for drug discovery programs in malaria and other infectious diseases

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table