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Venkatraman Srinivasan Radhakrishnan,1,2 Mohana Krishna Reddy Mudiam,3 Manish Kumar,1,2 Surya Prakash Dwivedi,4 Surinder Pal Singh,5 Tulika Prasad1,2 1Advanced Instrumentation Research and Facility (AIRF), Jawaharlal Nehru University (JNU), New Delhi, Delhi, India; 2Special Centre for Nano Sciences (SCNS), Jawaharlal Nehru University (JNU), New Delhi, Delhi, India; 3Analytical Chemistry Lab, Council for Scientific and Industrial Research (CSIR)-Indian Institute of Toxicology Research (IITR), Lucknow, Uttar Pradesh, India; 4School of Biotechnology, IFTM University, Moradabad, Uttar Pradesh, India; 5CSIR-National Physical Laboratory (NPL), New Delhi, Delhi, India Purpose: A significant increase in the incidence of fungal infections and drug resistance has been observed in the past decades due to limited availability of broad-spectrum antifungal drugs. Nanomedicines have shown significant antimicrobial potential against various drug-resistant microbes. Silver nanoparticles (AgNps) are known for their antimicrobial properties and lower host toxicity; however, for clinical applications, evaluation of their impact at cellular and molecular levels is essential. The present study aims to understand the cellular and molecular mechanisms of AgNp-induced toxicity in a common fungal pathogen, Candida albicans. Methods: AgNps were synthesized by chemical reduction method and characterized using UV–visible spectroscopy, X-ray powder diffraction, transmission electron microscopy, scanning electron microscopy–energy dispersive X-ray spectroscopy, energy dispersive X-ray fluorescence, and zeta potential. The anti-Candida activity of AgNps was assessed by broth microdilution and spot assays. Effects of AgNps on cellular and molecular targets were assessed by monitoring the intracellular reactive oxygen species (ROS) production in the absence and presence of natural antioxidant, changes in surface morphology, cellular ultrastructure, membrane microenvironment, membrane fluidity, membrane ergosterol, and fatty acids. Results: Spherical AgNps (10–30 nm) showed minimum inhibitory concentration (minimum concentration required to inhibit the growth of 90% of organisms) at 40 µg/mL. Our results demonstrated that AgNps induced dose-dependent intracellular ROS which exerted antifungal effects; however, even scavenging ROS by antioxidant could not offer protection from AgNp mediated killing. Treatment with AgNps altered surface morphology, cellular ultrastructure, membrane microenvironment, membrane fluidity, ergosterol content, and fatty acid composition, especially oleic acid. Conclusion: To summarize, AgNps affected multiple cellular targets crucial for drug resistance and pathogenicity in the fungal cells. The study revealed new cellular targets of AgNps which include fatty acids like oleic acid, vital for hyphal morphogenesis (a pathogenic trait of Candida). Yeast to hypha transition being pivotal for virulence and biofilm formation, targeting virulence might emerge as a new paradigm for developing nano silver-based therapy for clinical applications in fungal therapeutics. Keywords: AgNps, nanomedicine, drug resistance, membrane fluidity, antifungals, reactive oxygen species, ROS

Manjri Singh,1 Parul Gupta,2 Richa Baronia,1 Priti Singh,1 Stalin Karuppiah,1 Rishi Shankar,3 Premendra D Dwivedi,2 Surinder P Singh1 1CSIR-National Physical Laboratory, New Delhi, 2CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, 3Institute of Life Sciences, Ahmedabad University, Ahmedabad, Gujarat, India Abstract: We have synthesized graphene oxide (GO) nanosheets using modified Hummer’s method and conjugated it with doxorubicin (DOx), an anticancer drug. Drug release kinetics from GO–DOx conjugate indicated the drug release at acidic pH. MTT assay performed on FaDu hypopharyngeal cancer cell lines revealed that the GO–DOx nanoconjugate inhibited cell proliferation more efficiently compared with pure DOx. Preliminary results indicate the potential of designed GO–DOx drug conjugate for head and neck cancer. Keywords: graphene oxide, doxorubicin, nanomedicine, head and neck cancer

Rajni Singh,1 Mony Sreedharan Smitha,1 Stalin Karuppiah,2 Surinder P Singh2 1Amity Institute of Microbial Biotechnology, Amity University, Noida, Uttar Pradesh, 2CSIR-National Physical Laboratory, New Delhi, Delhi, India Abstract: GO with –OH, –CHO, –CO, –COOH, and epoxide groups is considered more suitable than other commonly used materials for biomedical applications. The presence of –CO, –CHO, and –OH groups renders the easy functionalization of GO by biomolecules and drugs. Therefore, in this study, we designed a multifunctional GO–Fe3O4 nanocomposite and investigated its bactericidal activity against different bacterial strains with an evaluation of percentage inhibition. Our results revealed the potential of GO–Fe3O4 nanocomposites as an effective bactericidal, which can be used for dynamic applications in medical devices and food and other industries. Keywords: graphene oxide, GO nanocomposites, GO–Fe3O4, pathogenic strains, antibacterial

Richa Baronia,1 Manjri Singh,1 Rajat B Gupta,1 Stalin Karuppiah,1 Rajiv Kumar,2 Jodi Belz,2 Rishi Shanker,3 Srinivas Sridhar,2 Surinder P Singh1 1CSIR-National Physical Laboratory, Dr KS Krishnan Marg, New Delhi, India; 2Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA; 3Institute of Life Sciences, Ahmedabad University, Ahmedabad, India Abstract: Gold nanoparticles, because of their high radiation absorption coefficient and efficient generation of secondary photoelectrons, have been predicted to enhance therapeutic efficacy in radiation therapy. However, high dose for effective treatment limits their use. We have synthesized multifunctional gold nanoclusters (GNCs) that can be used for imaging and radiation therapy. The designed GNCs have been characterized for their physicochemical properties, biocompatibility, and their radiation dose enhancement potential on PC3 cell lines. Keywords: gold nanoclusters, radiation therapy

Parul Gupta,1 Manjri Singh,2 Rajiv Kumar,3 Jodi Belz,3 Rishi Shanker,4 Premendra D Dwivedi,1 Srinivas Sridhar,3 Surinder P Singh2 1CSIR-Indian Institute of Toxicological Research, Lucknow, 2CSIR-National Physical Laboratory, New Delhi, India; 3Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA; 4Institute of Life Sciences, Ahmedabad University, Ahmedabad, India Abstract: Advances in nanotechnology have led to the design of multifunctional nanoparticles capable of cellular imaging, targeted drug delivery, and diagnostics for early cancer detection. We synthesized poly(lactic-co-glycolic acid) nanoparticles encapsulating a model radiosensitizing drug docetaxel accomplishing localized in situ delivery of the sensitizer to the tumor site. The synthesized nanoparticles have been characterized for their physicochemical properties. The in vitro cytotoxicity of drug-loaded nanoparticles has been studied on human tongue carcinoma cell line SCC-9 (ATCC-CRL-1629). Keywords: docetaxel, PLGA nanoformulation

Surinder P Singh,1 Rishi Shanker,2 Srinivas Sridhar,3 Thomas J Webster3 1CSIR-National Physical Laboratory, New Delhi, India; 2School of Arts & Sciences, Ahmedabad University, Ahmedabad, India; 3College of Engineering, Northeastern University, Boston, USA In the 21st century, nanomedicine is one of the fastest growing research areas in medicine and is expected to revolutionize health care by developing innovative diagnostic and therapeutic tools. In this context, an International Conference on Translational Nanomedicine (T-NANO 2014) was jointly organized by the CSIR-National Physical Laboratory, New Delhi, India; Northeastern University, Boston, USA; and the Institute of Life Sciences (ILS), Ahmedabad University, Ahmedabad, India, under the auspices of the IUSSTF-funded Indo-US Joint Centre on Nanomedicine for Head and Neck Cancer, Ahmedabad, from December 15–17, 2014. Center partners included Northeastern University; DFCI, Harvard Medical School, USA; CSIR-National Physical Laboratory; the CSIR-Indian Institute of Toxicology Research, Lucknow, India; the All India Institute of Medical Sciences, New Delhi, India; and the ILS. The central theme of the conference was to discuss the recent developments in nanotherapeutics, theranostics, nanomedicines, regenerative medicine, tissue engineering, diagnostics and imaging, toxicology, models for disease biology, and commercialization of all nanomedicines. The topics covered provided an understanding of how nanomaterials and nanotechnologies have played a pivotal role in advancing our understanding of biomedicine and in generating new tools toward the goal of improving human health.

Introduction: For better outcomes in mother and child health, Government of India launched the National Rural Health Mission (NRHM) in 2005 with a major objective of providing accessible, affordable and quality health care to the rural population; especially the vulnerable. Reduction in MMR to 100/100,000 is one of its goals and the Janani Suraksha Yojana (JSY) is the key strategy of NRHM to achieve this reduction. The JSY, as a safe motherhood intervention and modified alternative of the National Maternity Benefit Scheme (NMBS), has been implemented in all states and Union territories with special focus on low performing states. The main objective and vision of JSY is to reduce maternal, neo-natal mortality and promote institutional delivery among the poor pregnant women of rural and urban areas. This scheme is 100% centrally sponsored and has an integrated delivery and post delivery care with the help of a key person i.e. ASHA (Accredited Social Health Activist), followed by cash monetary help to the women. Objectives: 1)To evaluate cash benefit service provided under JSY at different health care settings. 2) To know the perception and elicit suggestions of beneficiaries on quality of cash benefit scheme of JSY. Methodology: This is a health care institute based observational cross sectional study including randomly selected 200 JSY beneficiary mothers from the different health care settings i.e., Primary Health Centres, Community Health Centres, District Hospital and Medical College Hospital of Rewa District of Madhya Pradesh state. Data was collected with the help of set pro forma and then analysed with Epi Info 2000. Chi square test was applied appropriately. Results: 60% and 80% beneficiaries from PHC and CHC received cash within 1 week after discharge whereas 100% beneficiaries of District Hospital and Medical College Hospital received cash at the time of discharge; the overall distribution of time of cash disbursement among beneficiaries of PHC, CHC, DH and Medical College Hospital were found to be statistically significant.(Chi-square =45.04, p-value: 0.0000). Shortage of doctors at Health Care Centers was found to be a major cause for the delay in cash disbursement.

β-catenin has two different cellular functions: intercellular adhesion and transcriptional activity. The E3 ubiquitin ligase Siah1 causes ubiquitin-mediated degradation of the cytosolic β-catenin and therefore, impairs nuclear translocation and oncogenic function of β-catenin. However, the effect of Siah1 on the cell membrane bound β-catenin has not been studied. In this study, we identified that the carcinogenic bacterium H. pylori increased ETS2 transcription factor-mediated Siah1 protein expression in gastric cancer cells (GCCs) MKN45, AGS and Kato III. Siah1 protein level was also noticeably higher in gastric adenocarcinoma biopsy samples as compared to non-cancerous gastric epithelia. Siah1 knockdown significantly decreased invasiveness and migration of H. pylori-infected GCCs. Although, Siah1 could not increase degradation of the cytosolic β-catenin and its nuclear translocation, it enhanced degradation of the membrane-bound β-catenin in the infected GCCs. This loss of membrane-bound pool of β-catenin was not associated with the proteasomal degradation of E-cadherin. Thus, this work delineated the role of Siah1 in increasing invasiveness of H. pylori-infected GCCs.

For better outcomes in mother and child health, Government of India launched the National Rural Health Mission (NRHM) in 2005 with a major objective of providing accessible, affordable and quality health care to the rural population; especially the vulnerable. Reduction in MMR to 100/100,000 is one of its goals and the Janani Suraksha Yojana (JSY) is the key strategy of NRHM to achieve this reduction. The JSY, as a safe motherhood intervention and modified alternative of the National Maternity Benefit Scheme (NMBS), has been implemented in all states and Union territories with special focus on low performing states. The main objective and vision of JSY is to reduce maternal, neo-natal mortality and promote institutional delivery among the poor pregnant women of rural and urban areas. This scheme is 100% centrally sponsored and has an integrated delivery and post delivery care with the help of a key person i.e. ASHA (Accredited Social Health Activist), followed by cash monetary help to the women. Objectives: 1)To evaluate cash benefit service provided under JSY at different health care settings. 2) To know the perception and elicit suggestions of beneficiaries on quality of cash benefit scheme of JSY. Methodology: This is a health care institute based observational cross sectional study including randomly selected 200 JSY beneficiary mothers from the different health care settings i.e., Primary Health Centres, Community Health Centres, District Hospital and Medical College Hospital of Rewa District of Madhya Pradesh state. Data was collected with the help of set pro forma and then analysed with Epi Info 2000. Chi square test was applied appropriately. Results: 60% and 80% beneficiaries from PHC and CHC received cash within 1 week after discharge whereas 100% beneficiaries of District Hospital and Medical College Hospital received cash at the time of discharge; the overall distribution of time of cash disbursement among beneficiaries of PHC, CHC, DH and Medical College Hospital were found to be statistically significant.(Chi-square =45.04, p-value: 0.0000). Shortage of doctors at Health Care Centers was found to be a major cause for the delay in cash disbursement.

In this work, we have developed a serial-chain multibody model of a rail vehicle, using the Decoupled Natural Orthogonal Complement matrices. The governing equations of the system were linearized, and the start of hunting was identified by finding the Smallest Bifurcation Point (SBP) of the trivial solution. Uneven wear creates differences in the properties of similar components in a rail vehicle. It was found that such variations are neglected in the hunting analysis. Hence, we introduce these differences by independently changing 32 parameters. The study found that these variations lead to unique trends. Then, these trends were used to recommend design changes for a rail vehicle, which could be thought of, in order to improve the hunting characteristics. For this purpose, an interactive software tool was created to easily visualize, and manipulate the hunting behavior of a rail vehicle. [ABSTRACT FROM AUTHOR]