Green's functions and Hadamard parametrices for vector and tensor fields in general linear covariant gauges

We determine the retarded and advanced Green’s functions and Hadamard parametrices in curved spacetimes for linearized massive and massless gauge bosons and linearized Einstein gravity with a cosmological constant in general linear covariant gauges. These vector and tensor parametrices contain additional singular terms compared with their Feynman/de Donder-gauge counterpart. We also give explicit recursion relations for the Hadamard coefficients, and indicate their generalization to n dimensions. Furthermore, we express the divergence and trace of the vector and tensor Green’s functions in terms of derivatives of scalar and vector Green’s functions, and show how these relations appear as Ward identities in the free quantum theory

Antitumor effect of IP-10 by using two different approaches: Live delivery system and gene therapy

Purpose: Immunotherapy is one of the treatment strategies for breast cancer, the most common cancer in women worldwide. In this approach, the patient�s immune system is stimulated to attack microscopic tumors and control metastasis. Here, we used interferon γ-induced protein 10 (IP-10), which induces and strengthens antitumor immunity, as an immunotherapeutic agent. We employed Leishmania tarentolae, a nonpathogenic lizard parasite that lacks the ability to persist in mammalian macrophages, was used as a live delivery system for carrying the immunotherapeutic agent. It has been already shown that arginase activity, and consequently, polyamine production, are associated with tumor progression. Methods: A live delivery system was constructed by stable transfection of pLEXSY plasmid containing the IP-10-enhanced green fluorescent protein (IP-10- egfp) fusion gene into L. tarentolae. Then, the presence of the IP-10-egfp gene and the accurate integration location into the parasite genome were confirmed. The therapeutic efficacy of IP- 10 delivered via L. tarentolae and recombinant pcDNA-(IP- 10-egfp) plasmid was compared by determining the arginase activity in a mouse 4T1 breast cancer model. Results: The pcDNA- (IP-10-egfp) group showed a significant reduction in tumor weight and growth. Histological evaluation also revealed that only this group demonstrated inhibition of metastasis to the lung tissue. The arginase activity in the tissue of the pcDNA-(IP- 10-egfp) mice significantly decreased in comparison with that in normal mice. No significant difference was observed in arginase activity in the sera of mice receiving other therapeutic strategies. Conclusion: Our data indicates that IP-10 immunotherapy is a promising strategy for breast cancer treatment, as shown in the 4T1-implanted BALB/c mouse model. However, the L. tarentolae- (IP-10-EGFP) live delivery system requires dose modifications to achieve efficacy in the applied regimen (six injections in 3 weeks). Our results indicate that the arginase assay could be a good biomarker to differentiate tumoral tissues from the normal ones. © 2016 Korean Breast Cancer Society. All rights reserved

C-Terminal Domain Deletion Enhances the Protective Activity of cpa/cpb Loaded Solid Lipid Nanoparticles against Leishmania major in BALB/c Mice

Cutaneous leishmaniasis (CL) is the most common form of leishmaniasis with an annual incidence of approximately 2 million cases and is endemic in 88 countries, including Iran. CL's continued spread, along with rather ineffectual treatments and drug-resistant variants emergence has increased the need for advanced preventive strategies. We studied Type II cysteine proteinase (CPA) and Type I (CPB) with its C-terminal extension (CTE) as cocktail DNA vaccine against murine and canine leishmaniasis. However, adjuvants' success in enhancing immune responses to selected antigens led us to refocus our vaccine development programs. Herein, we discuss cationic solid lipid nanoparticles' (cSLN) ability to improve vaccine-induced protective efficacy against CL and subsequent lesion size and parasite load reduction in BALB/c mice. For this work, we evaluated five different conventional as well as novel parasite detection techniques, i.e., footpad imaging, footpad flowcytometry and lymph node flowcytometry for disease progression assessments. Vaccination with cSLN-cpa/cpb-CTE formulation showed highest parasite inhibition at 3-month post vaccination. Immunized mice showed reduced IL-5 level and significant IFN-ã increase, compared to control groups. We think our study represents a potential future and a major step forward in vaccine development against leishmaniasis

Nutrition and lung cancer: a case control study in Iran

Background: Despite many prospective and retrospective studies about the association of dietary habit and lung cancer, the topic still remains controversial. So, this study aims to investigate the association of lung cancer with dietary factors. Method: In this study 242 lung cancer patients and their 484 matched controls on age, sex, and place of residence were enrolled between October 2002 to 2005. Trained physicians interviewed all participants with standardized questionnaires. The middle and upper third consumer groups were compared to the lower third according to the distribution in controls unless the linear trend was significant across exposure groups. Result: Conditional logistic regression was used to evaluate the association with lung cancer. In a multivariate analysis fruit (Ptrend < 0.0001), vegetable (P = 0.001) and sunflower oil (P = 0.006) remained as protective factors and rice (P = 0.008), bread (Ptrend = 0.04), liver (P = 0.004), butter (Ptrend = 0.04), white cheese (Ptrend < 0.0001), beef (Ptrend = 0.005), vegetable ghee (P < 0.0001) and, animal ghee (P = 0.015) remained as risk factors of lung cancer. Generally, we found positive trend between consumption of beef (P = 0.002), bread (P < 0.0001), and dairy products (P < 0.0001) with lung cancer. In contrast, only fruits were inversely related to lung cancer (P < 0.0001). Conclusion: It seems that vegetables, fruits, and sunflower oil could be protective factors and bread, rice, beef, liver, dairy products, vegetable ghee, and animal ghee found to be possible risk factors for the development of lung cancer in Iran

DNA plasmid coding for Phlebotomus sergenti salivary protein PsSP9, a member of the SP15 family of proteins, protects against Leishmania tropica

Background: The vector-borne disease leishmaniasis is transmitted to humans by infected female sand flies, which transmits Leishmania parasites together with saliva during blood feeding. In Iran, cutaneous leishmaniasis (CL) is caused by Leishmania (L.) major and L. tropica, and their main vectors are Phlebotomus (Ph.) papatasi and Ph. sergenti, respectively. Previous studies have demonstrated that mice immunized with the salivary gland homogenate (SGH) of Ph. papatasi or subjected to bites from uninfected sand flies are protected against L. major infection. Methods and results: In this work we tested the immune response in BALB/c mice to 14 different plasmids coding for the most abundant salivary proteins of Ph. sergenti. The plasmid coding for the salivary protein PsSP9 induced a DTH response in the presence of a significant increase of IFN-γ expression in draining lymph nodes (dLN) as compared to control plasmid and no detectable PsSP9 antibody response. Animals immunized with whole Ph. sergenti SGH developed only a saliva-specific antibody response and no DTH response. Mice immunized with whole Ph. sergenti saliva and challenged intradermally with L. tropica plus Ph. sergenti SGH in their ears, exhibited no protective effect. In contrast, PsSP9-immunized mice showed protection against L. tropica infection resulting in a reduction in nodule size, disease burden and parasite burden compared to controls. Two months post infection, protection was associated with a significant increase in the ratio of IFN-γ to IL-5 expression in the dLN compared to controls. Conclusion: This study demonstrates that while immunity to the whole Ph. sergenti saliva does not induce a protective response against cutaneous leishmaniasis in BALB/c mice, PsSP9, a member of the PpSP15 family of Ph. sergenti salivary proteins, provides protection against L. tropica infection. These results suggest that this family of proteins in Ph. sergenti, Ph. duboscqi and Ph. papatasi may have similar immunogenic and protective properties against different Leishmania species. Indeed, this anti-saliva immunity may act as an adjuvant to accelerate the cell-mediated immune response to co-administered Leishmania antigens, or even cause the activation of infected macrophages to remove parasites more efficiently. These findings highlight the idea of applying arthropod saliva components in vaccination approaches for diseases caused by vector-borne pathogens. © 2019, Public Library of Science. All rights reserved

Conformational Changes Associated with Activation of the Yeast Saccharomyces cerevisiae α-factor Receptor Ste2p

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Biochemistry and Biophysics, 2011.Activation of G-protein coupled receptors (GPCRs) by ligands results in nucleotide exchange by cytoplasmic G-proteins. We have developed a procedure for identifying functionally important conformational changes that occur upon activation of GPCRs. These studies have focused on Ste2p, a GPCR that activates the yeast pheromone response pathway in response to binding of the pheromone α-factor. To identify regions of Ste2p that undergo relative motion upon activation we screened for mutants with disulfide bonds that lock receptors in an activated state. We developed a mutagenic procedure that randomly introduces cysteine residues into targeted regions of a starting allele of Ste2p that completely lacks cysteines. Random cysteine mutagenesis performed on the fifth and sixth transmembrane (TM) segments of the -factor receptor led to the recovery of constitutively active mutants containing one cysteine in each segment. A role for disulfide bonds in the activation of these mutants is supported by dependence of constitutive signaling on the presence of two introduced cysteines, by a decrease in constitutive signaling caused by reducing agents, and by detection of crosslinked CNBr-cleaved receptor peptides by immunoblotting. We employed the ability of dTA, an α-factor analogue, to discriminate between constitutive and non-constitutive receptors. Antagonist binding to constitutive crosslinked receptors confirmed that, these receptors can be further activated by ligand and are present on the cell surface. Additional sites of crosslinking between TM segments 5 and 6 of Ste2p have also been detected, though none of these lead to receptor activation. These results indicate that relative motion of the TM5 and TM6 in the extracellular half of the membrane is sufficient to activate the receptor and that TM6, but not TM5, can undergo substantial rotational mobility that is not associated with receptor activation. Other TM segment (TM 3-6, TM 5-3 and TM 6-7) combinations were screened for disulfide crosslinks that lead to constitutive activity. However, no additional disulfide dependent constitutive mutants were identified from these screens. In an ongoing experiment, we are attempting to determine whether there is a common mechanism of activation between Ste2p and mammalian GPCRs, by introducing cysteine mutations at positions similar to those identified in Ste2p

Step by step analyzing, modeling and simulation of single and double array PV system in different environmental variability

This research analyses the mathematical model of the PV array with all the parameters involved, in the sequential steps. Then it is going to simulate the I-V and P-V characteristics of PV array in different climatology conditions, by using both MATLAB M-file and Simulink. Finally the capability of this method is demonstrated in simulated results, which are performed for both Single and Double Array PV system

Novel cyclic thiourea derivatives of aminoalcohols at the presence of AlCl3 catalyst as potent alpha-glycosidase and alpha-amylase inhibitors: Synthesis, characterization, bioactivity investigation and molecular docking studies

The article is devoted to the targeted synthesis and study of cyclic thiourea and their various new derivatives as new organic compounds containing polyfunctional group in the molecule. First time the reaction of the corresponding synthesized pyrimidinethione with 1,2-epoxy-3-chlorpropane at the presence of AlCl3 catalyst in 75-80 yield alkyl-1-(3-chloro-2-hydroxypropyl)-4-alkyl-6-phenyl-2-thioxo-1,2,5,6- tetrahydropyrimidine-5-carboxylates. In the next stage, new cyclic thiourea derivatives of aminoalcohols were synthesised from the reaction of chlorinated derivatives of pyrimidinethiones with single amines and their structures were investigated by spectroscopic methods. In this study, a series of novel compounds were tested towards some metabolic enzymes including alpha-glycosidase (alpha-Gly) and alpha-amylase (alpha-Amy) enzymes. Novel compounds showed Kis in ranging of 10.43 +/- 0.94-111.37 +/- 13.25 microM on alpha-glycosidase and IC50 values in ranging of 14.38-106.51 microM on alpha-amylase. The novel cyclic thiourea derivatives of aminoalcohols had effective inhibition profiles against all tested metabolic enzymes. Binding affinity and inhibition mechanism of the most active compounds were detected with in silico studies and have shown that 2-Hydroxypropyl and butan-1-aminium moieties play a key role for inhibition of the enzymes