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      • Piezoelectric non-linearity in PbSc<sub>0.5</sub>Ta<sub>0.5</sub>O<sub>3</sub> thin films

        Chopra, A.,Kim, Y.,Alexe, M.,Hesse, D. Pergamon Press 2014 The Journal of physics and chemistry of solids Vol.75 No.11

        Epitaxial (001)-oriented PbSc<SUB>0.5</SUB>Ta<SUB>0.5</SUB>O<SUB>3</SUB> (PST) thin films were deposited by pulsed laser deposition. Local piezoelectric investigations performed by piezoelectric force microscopy show a dual slope for the piezoelectric coefficient. A piezoelectric coefficient of 3pm/V was observed at voltages up to 0.8V. However, at voltages above 0.8V, there is a steep increase in piezoelectric coefficient mounting to 23.2pm/V. This nonlinear piezoelectric response was observed to be irreversible in nature. In order to better understand this nonlinear behavior, voltage dependent dielectric constant measurements were performed. These confirmed that the piezoelectric non-linearity is indeed a manifestation of a dielectric non-linearity. In contrast to classical ferroelectric systems, the observed dielectric non-linearity in this relaxor material cannot be explained by the Rayleigh model. Thus the dielectric non-linearity in the PST films is tentatively explained as a manifestation of a percolation of the polar nano regions.

      • Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase ½ dose escalation and expansion trial

        El-Khoueiry, A.B.,Sangro, B.,Yau, T.,Crocenzi, T.S.,Kudo, M.,Hsu, C.,Kim, T.Y.,Choo, S.P.,Trojan, J.,Welling, T.H.,Meyer, T.,Kang, Y.K.,Yeo, W.,Chopra, A.,Anderson, J.,dela Cruz, C.,Lang, L.,Neely, J. J. Onwhyn ; Elsevier Science Ltd 2017 The Lancet Vol.389 No.10088

        Background: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. Methods: We did a phase ½, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection. Previous sorafenib treatment was allowed. A dose-escalation phase was conducted at seven hospitals or academic centres in four countries or territories (USA, Spain, Hong Kong, and Singapore) and a dose-expansion phase was conducted at an additional 39 sites in 11 countries (Canada, UK, Germany, Italy, Japan, South Korea, Taiwan). At screening, eligible patients had Child-Pugh scores of 7 or less (Child-Pugh A or B7) for the dose-escalation phase and 6 or less (Child-Pugh A) for the dose-expansion phase, and an Eastern Cooperative Oncology Group performance status of 1 or less. Patients with HBV infection had to be receiving effective antiviral therapy (viral load <100 IU/mL); antiviral therapy was not required for patients with HCV infection. We excluded patients previously treated with an agent targeting T-cell costimulation or checkpoint pathways. Patients received intravenous nivolumab 0.1-10 mg/kg every 2 weeks in the dose-escalation phase (3+3 design). Nivolumab 3 mg/kg was given every 2 weeks in the dose-expansion phase to patients in four cohorts: sorafenib untreated or intolerant without viral hepatitis, sorafenib progressor without viral hepatitis, HCV infected, and HBV infected. Primary endpoints were safety and tolerability for the escalation phase and objective response rate (Response Evaluation Criteria In Solid Tumors version 1.1) for the expansion phase. This study is registered with ClinicalTrials.gov, number NCT01658878. Findings: Between Nov 26, 2012, and Aug 8, 2016, 262 eligible patients were treated (48 patients in the dose-escalation phase and 214 in the dose-expansion phase). 202 (77%) of 262 patients have completed treatment and follow-up is ongoing. During dose escalation, nivolumab showed a manageable safety profile, including acceptable tolerability. In this phase, 46 (96%) of 48 patients discontinued treatment, 42 (88%) due to disease progression. Incidence of treatment-related adverse events did not seem to be associated with dose and no maximum tolerated dose was reached. 12 (25%) of 48 patients had grade ¾ treatment-related adverse events. Three (6%) patients had treatment-related serious adverse events (pemphigoid, adrenal insufficiency, liver disorder). 30 (63%) of 48 patients in the dose-escalation phase died (not determined to be related to nivolumab therapy). Nivolumab 3 mg/kg was chosen for dose expansion. The objective response rate was 20% (95% CI 15-26) in patients treated with nivolumab 3 mg/kg in the dose-expansion phase and 15% (95% CI 6-28) in the dose-escalation phase. Interpretation: Nivolumab had a manageable safety profile and no new signals were observed in patients with advanced hepatocellular carcinoma. Durable objective responses show the potential of nivolumab for treatment of advanced hepatocellular carcinoma. Funding: Bristol-Myers Squibb.

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        T-regulatory cells are relatively deficient in squamous carcinomas undergoing regression in mice immunized with a squamous carcinoma vaccine enriched for immunotherapeutic cells

        Chopra, A,O-Sullivan, I,Carr, J,Kim, T S,Cohen, E P Nature Publishing Group 2007 Cancer gene therapy Vol.14 No.6

        In a prior report (Int J Cancer 2006; 119: 339–348), we described a new vaccination strategy for squamous cell carcinoma (SCC). The vaccine was prepared by transfer of unfractionated DNA-fragments (25 kb) from KLN205 cells, a squamous carcinoma cell line (DBA/2 origin; H-2<SUP>d</SUP>) into LM cells, a highly immunogenic mouse fibroblast cell line (C3H/He origin; (H-2<SUP>k</SUP>)). As only a small proportion of the transfected cell population was expected to have incorporated DNA segments that included genes specifying antigens associated with the squamous carcinoma cells, we devised a novel strategy to enrich the vaccine for immunotherapeutic cells. Enhanced immunity to squamous carcinoma was induced in tumor-bearing mice treated solely by immunization with the enriched vaccine, which translated into prolonged survival without toxicity. Here, we describe the characteristics of the cell populations infiltrating established squamous carcinomas undergoing regression in mice immunized with vaccines enriched for immunotherapeutic cells. The results indicated that CD8+ T cells were predominant and that T-regulatory cells (FoxP3+, CD4/CD25+, CD4/CD62L<SUP>high</SUP>, CD4/CTLA-4e) were relatively deficient in the regressing tumors. Inflammatory infiltrates were not detected in various organs and tissues of mice immunized with the DNA-based vaccine.Cancer Gene Therapy (2007) 14, 573–582. doi:10.1038/sj.cgt.7701040; published online 23 March 2007

      • SCISCIESCOPUS

        New strategy for the identification of squamous carcinoma antigens that induce therapeutic immune responses in tumor-bearing mice

        O-Sullivan, I,Chopra, A,Kim, T S,Magnuson, S,Falduto, M T,Huang, J,Cohen, E P Nature Publishing Group 2007 Cancer gene therapy Vol.14 No.4

        This study describes a new strategy for the identification of squamous carcinoma antigens tumor-associated antigens (TAA). The antigens were discovered by comparing microarrays of squamous carcinoma vaccines highly enriched for immunotherapeutic cells with non-enriched vaccines. The vaccines were prepared by transferring sheared genomic DNA fragments (25 kb) from KLN205 cells, a squamous carcinoma cell line (DBA/2 mouse origin (H-2<SUP>d</SUP>) into LM fibroblasts (C3H/He origin, H-2<SUP>k</SUP>). The transferred tumor DNA segments integrate spontaneously into the genome of the recipient cells, replicate as the cells divide and are expressed. As only a small proportion of the transfected cell population was expected to have incorporated DNA segments that included genes specifying TAA (the vast majority specify normal cellular constituents), a novel strategy was employed to enrich the vaccine for TAA-positive cells. Microarrays were used to compare genes expressed by enriched and non-enriched vaccines. Seventy-five genes were overexpressed in cells from the enriched vaccine. One, the gene for Cytochrome P450 (family 2, subfamily e, polypeptide 1) (Cyp2e1), was overexpressed in the enriched but not the non-enriched vaccine. A vaccine for squamous carcinoma was prepared by transfer of a 357 bp fragment of the gene for Cyp2e1 into the fibroblast cell line. Robust immunity, sufficient to result in indefinite survival, was induced in tumor-bearing mice immunized with cells transfected with this gene fragment.Cancer Gene Therapy (2007) 14, 389–398. doi:10.1038/sj.cgt.7701023; published online 2 February 2007

      • SCISCIESCOPUS
      • SCIESCOPUSKCI등재

        Phenotypic Characterization and Multivariate Analysis to Explain Body Conformation in Lesser Known Buffalo (Bubalus bubalis) from North India

        Vohra, V.,Niranjan, S.K.,Mishra, A.K.,Jamuna, V.,Chopra, A.,Sharma, Neelesh,Jeong, Dong Kee Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.3

        Phenotypic characterization and body biometric in 13 traits (height at withers, body length, chest girth, paunch girth, ear length, tail length, length of tail up to switch, face length, face width, horn length, circumference of horn at base, distances between pin bone and hip bone) were recorded in 233 adult Gojri buffaloes from Punjab and Himachal Pradesh states of India. Traits were analysed by using varimax rotated principal component analysis (PCA) with Kaiser Normalization to explain body conformation. PCA revealed four components which explained about 70.9% of the total variation. First component described the general body conformation and explained 31.5% of total variation. It was represented by significant positive high loading of height at wither, body length, heart girth, face length and face width. The communality ranged from 0.83 (hip bone distance) to 0.45 (horn length) and unique factors ranged from 0.16 to 0.55 for all these 13 different biometric traits. Present study suggests that first principal component can be used in the evaluation and comparison of body conformation in buffaloes and thus provides an opportunity to distinguish between early and late maturing to adult, based on a small group of biometric traits to explain body conformation in adult buffaloes.

      • KCI등재

        Phenotypic Characterization and Multivariate Analysis to Explain Body Conformation in Lesser Known Buffalo (Bubalus bubalis) from North India

        V. Vohra,S.K. Niranjan,A.K. Mishra,V. Jamuna,A. Chopra,Neelesh Sharma,정동기 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.3

        Phenotypic characterization and body biometric in 13 traits (height at withers, body length, chest girth, paunch girth, ear length, tail length, length of tail up to switch, face length, face width, horn length, circumference of horn at base, distances between pin bone and hip bone) were recorded in 233 adult Gojri buffaloes from Punjab and Himachal Pradesh states of India. Traits were analysed by using varimax rotated principal component analysis (PCA) with Kaiser Normalization to explain body conformation. PCA revealed four components which explained about 70.9% of the total variation. First component described the general body conformation and explained 31.5% of total variation. It was represented by significant positive high loading of height at wither, body length, heart girth, face length and face width. The communality ranged from 0.83 (hip bone distance) to 0.45 (horn length) and unique factors ranged from 0.16 to 0.55 for all these 13 different biometric traits. Present study suggests that first principal component can be used in the evaluation and comparison of body conformation in buffaloes and thus provides an opportunity to distinguish between early and late maturing to adult, based on a small group of biometric traits to explain body conformation in adult buffaloes.

      • SCIESCOPUSKCI등재

        BLOOD METABOLITES LEVELS IN RELATION TO AGE AND LIVE WEIGHT IN YOUNG BUFFALO CALVES

        Sikka, P.,Sethi, R.K.,Tomer, A.K.S.,Chopra, S.C. Asian Australasian Association of Animal Productio 1994 Animal Bioscience Vol.7 No.2

        Thirty buffalo calves were randomly categorized into three groups on the basis of age, i.e. birth to 6 months; 6 to 12 months and 12-24 months. Blood samples were collected to monitor certain vital metabolites in relation to age and prediction of performance in growing buffalo calves. Amongst the various blood parameters estimated the serum glucose, cholesterol and gamma globulins have shown highly significant correlations with age and live weight-gain of the animal as well. However, the multiple regression analysis clearly indicated the influence of age and live body weight on blood metabolites in buffalo calves.

      • SCOPUSKCI등재

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