Anjali Singh - Academia.edu (original) (raw)

Papers by Anjali Singh

Journal of Virology, 1999

Human immunodeficiency virus type 1 (HIV-1) infection is highly compartmentalized, with distinct ... more Human immunodeficiency virus type 1 (HIV-1) infection is highly compartmentalized, with distinct viral genotypes being found in the lungs, brain, and other organs compared with blood. CCR5 and CXCR4 are the principal HIV-1 coreceptors, and a number of other molecules support entry in vitro but their roles in vivo are uncertain. To address the relationship between tissue compartmentalization and the selective use of entry coreceptors, we generated functional env clones from primary isolates derived from the lungs and blood of three infected individuals and analyzed their use of the principal, secondary, orphan, and virus-encoded coreceptors for fusion. All Env proteins from lung viruses used CCR5 but not CXCR4, while those from blood viruses used CCR5 or CXCR4 or both. The orphan receptor APJ was widely used for fusion by Env proteins from both blood and lung viruses, but none used the cytomegalovirus-encoded receptor US28. Fusion mediated by the secondary coreceptors CCR2b, CCR3, CC...

Blood, 2010

4342 Preclinical Studies of Cytotoxicity, Drug Synergy and Biological Correlates of Clofarabine A... more 4342 Preclinical Studies of Cytotoxicity, Drug Synergy and Biological Correlates of Clofarabine Against Infant Leukemia Cells. Infants with leukemia, specifically those who relapse on frontline therapy, are extremely difficult to cure and are candidates for novel therapies that induce remission, allowing them to proceed to transplantation. The unique molecular, growth and chemoresistance properties of infant acute lymphoblastic leukemia (iALL) allow for focused preclinical studies within this group. Clofarabine (Clolar), an anti-neoplastic purine nucleoside analog, has shown significant efficacy in older children with refractory lymphoblastic leukemia. Its safety profile has more recently been established in Phase I and II single-agent trials. In addition to its anti-metabolite action, clofarabine appears to disrupt the integrity of mitochondrial membranes and activates pathways of programmed cell death, adding to its theoretical potential to synergize with agents that interfere wit...

Drying is one of the most important unit operation applied for preservation of agricultural produ... more Drying is one of the most important unit operation applied for preservation of agricultural products. It reduces the water activity of the product making it less susceptible to microbial growth. Conventional drying techniques such as hot-air drying, fluidized bed drying etc. are highly energy-intensive and affect an array of physical and chemical characteristics of the product. Application of high drying temperature during conventional drying negatively impacts the nutritional and organoleptic properties of the products making it unsuitable for heat sensitive materials. Recent change in consumer demand for high quality products and increasing environmental concerns have led to application of novel techniques such as freeze drying, microwave, and radio-frequency either alone or in combination with conventional techniques to improve the efficiency and quality of the drying process. Electrohydrodynamic drying (EHD) is a method of inducing electric wind that is generated by gaseous ions under the influence of a high-voltage electric field. Impingement of the electric wind on the biological matrix disrupts the saturated air layer and promotes diffusion of water from within on to the surface of the matrix, leading to evaporation enhancement. Interaction of the ionic wind with the biochemical components such as protein, phenolic antioxidants and starch of the biological products and the quality parameters such as colour, texture and firmness is not well understood. The present paper relates the operational parameters of the EHD process with these organoleptic and nutritional properties of the product.

Journal of Experimental & Clinical Cancer Research, 2015

Background: Neuroblastoma (NB) is one of the most common childhood malignancies. Currently, high ... more Background: Neuroblastoma (NB) is one of the most common childhood malignancies. Currently, high risk NB carries a poor outcome and significant treatment related toxicities and, thus has been a focus for new therapeutics research in pediatric oncology. In this study, we evaluated the effects of the MEK inhibitor cobimetinib, as a single agent and in combinations, on the growth, survival and differentiation properties against a molecularly representative panel of NB cell lines. Methods: In vitro anti-proliferative activity of cobimetinib alone or in combination was investigated by cell viability assays and its target modulatory activity was evaluated using phospho-kinases antibody arrays and western blot analysis. To determine the effect of combination with cis-RA on differentiation and resulting enhanced cellular cytotoxicity, the expression of glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) expression levels were examined by immuno-fluorescence. Results: Our findings show that cobimetinib alone induced a concentration-dependent loss of cell viability in all NB cell lines. In addition, cobimetinib showed feedback activation of MEK1/2, and the dephosphorylation of extracellular signal-regulated kinases (ERK1/2) and c-RAF, providing information on the biological correlates of MEK inhibition in NB. Combined treatment with cis-RA, led to differentiation and enhanced sensitization of NB cells lines to cobimetinib. Conclusion: Collectively, our results provide evidence that cobimetinib, in combination with cis-RA, represents a feasible option to develop novel treatment strategies for refractory NB.

Virology, 2001

Several coreceptors in addition to CCR5 and CXCR4 support immunodeficiency virus entry in transfe... more Several coreceptors in addition to CCR5 and CXCR4 support immunodeficiency virus entry in transfected cells, but whether they could play a role in HIV-1 pathogenesis is uncertain. To probe whether human macrophages express potentially functional alternative entry pathways, we analyzed cell-cell fusion and infection of primary macrophage by several SIVmac Envs. All Envs fused with normal macrophages. One, SIVmac316, also fused efficiently with macrophages lacking CCR5. CCR5-independent fusion was not mediated by CXCR4 and was CD4 dependent, while CCR5-mediated fusion was partly independent of CD4. However, pseudotype virions carrying the SIVmac316 Env and HIV-1 core could not infect macrophages through the CCR5-independent pathway, although they did infect wild-type macrophages. Thus, human macrophages possess an alternative coreceptor pathway that mediates SIV Env fusion but does not support infection. Macrophage entry pathways other than CCR5 and CXCR4 may have limited potential in pathogenesis given their restricted capacity for infection despite efficient fusion.

AYU (An International Quarterly Journal of Research in Ayurveda), 2014

problem would be conquered. Since then, several antibiotics in the form of systemic and local use... more problem would be conquered. Since then, several antibiotics in the form of systemic and local use have been tried, but problems of chronic wound healing remain as such. Research on wound healing drugs is a potential area in biomedical sciences. Ayurveda, the Indian traditional system of medicine, mentions the values of many medicinal plants for wound healing. Scientists who are trying to explore newer drugs from natural resources are looking towards Ayurveda because phyto-medicines are not only affordable, but are comparatively safe also. Several drugs from plant, mineral, and animal origin are described in Ayurveda for their wound healing properties under the term Vranaropaka (wound healing agent). Wound healing activities of some plants have been screened scientifically in different pharmacological models and patients, but the potential of most of them still remains unexplored. Some Ayurvedic plants, namely Vata (Ficus bengalensis Linn.), Durva (Cynodon dactylon Pers.), Lodhra (Symplocos racemosa Roxb.), Manjishtha (Rubia cordifolia Linn.), Chandan (Pterocarpus santalinus Linn. f.), Gular (Ficus racemosa Roxb.), Yashtimadhu (Glycyrrhiza glabra Linn.), Daruharidra (Berberis aristata DC.

IETE Technical Review, 1985

Dispersion in Optical Fibres, describing the impulse response of the optical fibre for optimum tr... more Dispersion in Optical Fibres, describing the impulse response of the optical fibre for optimum transmission rates is of major concern in communication system design. The present state of understanding of the various dispersion models and characterization with appropriate measurement techniques have been reviewed with an aim to have a critical appraisal of the problems involved.

Aerial Surveillance Sensing Including Obscured and Underground Object Detection, 1994

CARABAS, an acronym for `coherent all radio band sensing,' is an airborne, horizontal-polariz... more CARABAS, an acronym for `coherent all radio band sensing,' is an airborne, horizontal-polarization SAR operating across the frequency band 20 to 90 MHz, conceived, designed and built by FOA in Sweden. The original motivation for designing such a low frequency system was that a large relative or fractional bandwidth could be achieved at low frequencies. For reasons to be explained, a large fractional bandwidth was considered to be of potential benefit for radar detection in severe clutter environments. A feasibility study of a short wave ultra-wideband radar started at FOA in 1985. Actual construction of the CARABAS system commenced 1987, aircraft integration took place during 1991 and the first radar tests were conducted in early 1992. From the fall of 1992 onwards, field campaigns and evaluation studies have been conducted as a joint effort between FOA and MIT Lincoln Laboratory in the US. This article will focus on experiences concerning foliage penetration with the system. First we touch upon the CARABAS system characteristics, outline the arguments behind a large fractional bandwidth VHF-band SAR approach to foliage penetration, and finally present some early experimental results. We refer to other papers for a fuller explanation of the system, for more details of image calibration, and for results concerning underground imaging.

SPIE Proceedings, 1999

An optimized long-wavelength two-color Quantum Well Infrared Photodetector (QWIP) device structur... more An optimized long-wavelength two-color Quantum Well Infrared Photodetector (QWIP) device structure has been designed. This device structure was grown on a threeinch semi-insulating GaAs substrate by molecular beam epitaxy (MBE). This wafer was processed into several 640x486 format monolithically integrated 8-9 and 14-1 5 pm twocolor (or dual wavelength) QWIP focal plane arrays (FPAs). These FPAs were then hybridized to 640x486 silicon CMOS readout multiplexers. A thinned (i.e., substrate removed) FPA hybrid was integrated into a liquid helium cooled dewar to perform electrical and optical characterization and to demonstrate simultaneous two-color imagery. The 8-9 pm detectors in the FPA have shown background limited performance (BLIP) at 70 K operating temperature, at 300 K background with f/2 cold stop. The 14-15 pm detectors of the FPA have reached BLIP at 40 K operating temperature at the same background conditions. In this presentation we discuss the performance of this longwavelength dualband QWIP FPA in quantum efficiency, detectivity, noise equivalent temperature difference (NEAT), uniformity, and operability.

Toxicology Letters, 1998

The present study was designed to elucidate the inhibitory potential of Momordica charantia (Bitt... more The present study was designed to elucidate the inhibitory potential of Momordica charantia (Bitter Gourd) peel, pulp, seed and whole fruit extract on mouse skin papillomagensis with the modulatory influence of biotransformation system enzymes. Topical application of Momordica whole fruit extract (100 vl/animal per day) during the peri-initiation stage (1 week before and 2 weeks after initiation) by 7,12-dimethylbenz[a]anthracene (DMBA) and/or during the tumor promotion stage reduced the (i) tumor burden to 4.26, 3.72 and 3.11 (positive control value: 5.42); (ii) cumulative number of papillomas to 81, 67 and 53 (positive control value: 103); and (iii) percent incidence of mice bearing papillomas to 100, 94 and 94, respectively (positive control value: 100). In a comparison of the anticarcinogenic efficacy of Momordica peel, pulp, seed and whole fruit extract (100 vl/animal per day), after topical treatment during the peri-initiation and during the tumor promotion stage, revealed the modulation of the (i) tumor burden (tumors/mouse) to 3.06, 3.61, 3.17 and 3.11; (ii) cumulative number of papillomas to 49, 65, 54 and 53; and (iii) percent incidence of mice bearing papillomas to 84, 100, 94 and 94, respectively. Significant elevation in the sulfhydryl (-SH) level was observed in the liver and skin tissues by the topical treatment of Momordica peel, pulp, seed and whole fruit extract. Elevation in the hepatic levels of cytosolic glutathione S-transferase (GST) and microsomal cytochrome b 5 was also observed by the topical treatment of Momordica peel, seed and whole fruit extract. The results suggest the maximum chemopreventive potential is in the Momordica peel. Equivocal efficacy is in the Momordica seed and whole fruit extract. Biotransformation system enzymes may be the cause of this reduced papillomagenesis.

International Journal of Scientific Research, 2012

Physics Letters A, 1998

ELSEVIER Physics Letters A 243 (1998) 335344 6 July 1998 PHYSICS LETTERS A Interaction between no... more ELSEVIER Physics Letters A 243 (1998) 335344 6 July 1998 PHYSICS LETTERS A Interaction between nonlinear electron waves Danhong Huang, DA Cardimona, Anjali Singh US Air Force Research Laboratory (AFRLNSSS), 3550 Aberdeen Avenue Southeast, Building 426, ...

Sex Roles, 1986

To test the selective recall hypothesis, male and female adolescents listened to a tape recording... more To test the selective recall hypothesis, male and female adolescents listened to a tape recording of 30 “findings” about sex differences. Fifteen of the findings were pro-female and 15 were anti-female. After being given free recall and then cued recall tests, the subjects completed the British version of the attitudes towards women scale. Multiple regression analysis supported the prediction that males, and those with more negative attitudes to wards women, recalled less pro-and more anti-female items, and vice versa. The ...

Physics Letters A, 1999

Based on an isotropic random distribution model, the effects of structural disorders embedded in ... more Based on an isotropic random distribution model, the effects of structural disorders embedded in the barriers on the sequential electron tunneling in multiple quantum wells were studied at low temperatures. By using a sequential tunneling model [Stievenard et al., Appl. Phys. ...

Pediatric Blood & Cancer, 2010

ABT-737 is a BH3 mimetic small-molecule inhibitor that binds with high affinity to Bcl-2 to induc... more ABT-737 is a BH3 mimetic small-molecule inhibitor that binds with high affinity to Bcl-2 to induce apoptosis in malignant cells and has shown promise as an effective anti-leukemic agent in pediatric preclinical tests. This study focuses on the effects of ABT-737 on leukemia cells with MLL rearrangement and identifies some of the biological correlates of its activity. Cells were cultured in the presence of increasing concentrations of ABT-737 alone or in combination with other agents. After 4 days in culture, cell growth inhibition was measured by Alamar blue assay. The expression and activation of potential intracellular targets of ABT-737 activity were determined by Western blot analysis. Significant Bcl-2 expression was detected in all infant leukemia cells investigated. ABT-737 induced cell death in all cell lines studied although the IC(50) values differed somewhat between cell lines. Western blot analysis identified the effects of ABT-737 on survival and apoptosis-regulatory proteins PARP, caspase-8, and cytochrome-c. Drug combination studies indicated synergy with distinct anti-neoplastic agents, including the multi-tyrosine kinase inhibitor sunitinib. This effective drug synergy appears to be mediated by the combined inhibition of Bcl-2 and intracellular signaling pathways. We describe the in vitro studies to demonstrate the activity and drug combinability of ABT-737 against MLL rearranged leukemia cells. In addition, identification of the molecular changes that occur in the presence of ABT-737 provides information regarding effective target validation and target modulation analyses in future clinical trials.

$Research paper thumbnail of Double-deleted vaccinia virus in virotherapy for refractory and metastatic pediatric solid tumors$

Molecular Oncology, 2013

Background: Previous studies have shown successful antitumor effects of systemically delivered do... more Background: Previous studies have shown successful antitumor effects of systemically delivered double-deleted vaccinia virus (vvDD) against a number of adult tumor models, including glioma, colon and ovarian cancers. The purpose of this study was to investigate the oncolytic potential of vvDD against a panel of cell lines representative of pediatric solid tumors that are currently difficult to cure. Methods: Cell lines derived from central nervous system atypical teratoid rhabdoid tumor (AT/RT) (BT12, BT16 and KCCF1), sarcoma (143B, HOS, RD and RH30), and neuroblastoma (SKNAS, SKNBE2, IMR-5 and IMR-32) were examined for vvDD mediated cytotoxicity defined by virus expansion followed by loss of tumor cell viability. The normal human fibroblast cell line HS68 was used as a control. Next, relevant orthotopic, subcutaneous and lung metastasis xenograft models were treated with intravenous doses of live vvDD or killed virus controls (DV). Tumor growth inhibition and viral replication were quantified and survival outcomes of these animals were assessed. Results: vvDD was able to infect and kill nine of eleven of the pediatric tumor cells (81.8%) in vitro. In xenograft models, intravenous administration of a single dose of vvDD significantly inhibited the growth of tumors and prolonged the survival of intracranial and metastatic tumors. Conclusions: Oncolytic vvDD administered i.v. shows activity in preclinical models of pediatric malignancies that are resistant to many currently available treatments. Our data support further evaluation of vvDD virotherapy for refractory pediatric solid tumors.

Leukemia Research, 2011

Although recent decades have seen a significant improvement in the treatment outcome of leukemia ... more Although recent decades have seen a significant improvement in the treatment outcome of leukemia in the pediatric population, those who are treated for relapsed disease still face significant morbidity and mortality. However, current salvage regimens are often assembled with agents that have similar mode of activity as the chemotherapeutics used in the initial treatment. Hence, novel therapeutic agents that are capable of distinct and diverse mechanisms of activity in, now resistant, leukemia cells are of great interest. We have investigated the opioid agonist methadone for its anti-leukemic activity, initially reported in studies with cell lines derived from adult patients. Our findings show that, compared to normal cells, methadone has enhanced cytotoxicity against specimens and cell lines established from refractory childhood leukemia. In addition, methadone's activity synergized with that of the anti-Bcl-2 agent ABT-737 and was characterized by the induction of distinct changes in tumor cell mitochondria. Data presented also identify biological correlates and a potential mechanism for methadone activity by its effects on Mcl-1 and other members of the apoptosis cascade. We provide mechanistic data for the therapeutic potential of a family of agents that is largely unexplored for anti-leukemic activity.

Journal of Virological Methods, 1999

HIV-1 cell tropism is determined initially at the level of fusion mediated by the viral envelope ... more HIV-1 cell tropism is determined initially at the level of fusion mediated by the viral envelope glycoprotein (Env). Cell-cell fusion assays are employed widely to study Env-mediated fusion, and generally require transfection of target cells with a reporter plasmid that is activated upon fusion with Env-expressing effector cells. Macrophages are an important target for HIV-1, but fusion studies using primary macrophages are limited by their resistance to transfection. An assay described previously used recombinant vaccinia virus to express T7 polymerase in macrophages, and effector cells transfected with a T7-driven reporter plasmid and infected with recombinant vaccinia virus expressing Env. However, this requires a recombinant vaccinia virus for each Env. We developed a method to study fusion using primary macrophages and HIV-1 env plasmid clones under control of the T7 promoter. Macrophages were infected with a recombinant vaccinia virus expressing the SP6 RNA polymerase. Effector 293T cells were infected with a recombinant vaccinia virus expressing T7 polymerase, and co-transfected with T7-driven env plasmids and an SP6-driven reporter gene plasmid. Cell-cell fusion mediated by T7-driven Env results in SP6-driven reporter gene transactivation. This approach is suitable for rapid analysis of multiple primary isolate, chimeric, or mutant env genes cloned into plasmid vectors.

Journal of Clinical Investigation, 1999

Methods Viruses. We used the dual-tropic R5X4 strain 89.6 and macrophage-tropic (Mtropic) R5 stra... more Methods Viruses. We used the dual-tropic R5X4 strain 89.6 and macrophage-tropic (Mtropic) R5 strains SF162 and JR-FL (21,