52 research outputs found

    Interplay of polymer and oligonucleotide properties in the nature of antisense effects

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    Antisense oligonucleotides can be utilized to silence the expression of a target gene via sequence-specific complementary base pairing. Antisense technology is applied as a basic research tool and is being developed therapeutically for a wide range of indications including cancer, inflammatory diseases and viral diseases. Its widespread application is impeded by the poor cellular delivery of oligonucleotides (ONs). Rational design of carriers for enhanced ON delivery demands a better understanding of the role of the vector on the extent and time course of antisense effects. This work highlights the interplay of polymer and ON properties in the nature of polymer mediated antisense responses. First, we demonstrate that ON structure exerts a significant influence on the strength of ON binding to, and dissociation from, the cationic polymer, poly-L-lysine. The finding implicates secondary structure as a relevant design parameter for antisense ONs and stresses the need for a comprehensive evaluation of ON-polymer structure-activity effects. Next, using well-characterized cationic polymer polyethyleneimine (PEI), we focus on understanding the effects of polymer molecular weight (MW) and ON backbone chemistry on antisense activity. We measure physico-chemical properties of complexes between PEI and phosphodiester and phosphorothioate backbone ONs, and evaluate their ability to deliver ONs to cells, leading to an antisense response. Our key finding is that the antisense activity is not determined solely by PEI MW or by ON chemistry, but rather by the interplay of both factors. Of particular importance is the strength of interactions between the carrier and the ON, which determines the rate at which the ONs are delivered intracellularly. Finally, we utilize the chemistry of the ONs as a means to influence the strength of interactions between PEI and ONs, and hence control the final antisense response. We show that it is possible to improve dramatically the efficiency of lower PEI MWs as ON carriers by manipulating the degree of phosphorothioate substitution in the ON chemistry. By correlating the PEI MW & ON chemistry with the observed antisense effects, we draw insightful structure-property relationships that will aid the rational design of ON carriers.Ph.D.Includes bibliographical references (p. 129-137)

    Doing Business in Asia

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    From the author of Doing Business in Europe (SAGE, 2018), Gabriele Suder has teamed up with Sumati Varma based in India, and Terence Tsai from China to bring this comprehensive solution for Asian business teaching and learning. The book offers a highly productive mix of international business and marketing theory, and is packed with pedagogical tools to engage and develop understanding, including two full-length corporate case studies per chapter. This is a unique volume covering the most relevant topics of Asia-focused business and management practice spanning from cross-cultural management to supply chain resilience to market entry and expansion strategy, and much more. Specifically designed to meet the needs of Postgraduate, MBA and those taking part in Executive Education programmes, this exciting learning experience will prepare Asia's leaders of the future

    Design and analysis of class E RF power amplifiers

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    The most important stage in a wireless transmitter is the power amplifier because this stage consumes a great deal of power in a wireless system and is a major factor in the battery life of portable equipment. Generally, switching RF power amplifiers have greater efficiency than their linear counterparts but they are also more difficult to analyze, have switching losses, and can introduce switching transients into the amplified signal. The research focus for this dissertation is on the Class E switching RF power amplifier. This circuit topology uses soft switching in order to minimize switching transients and achieve nearly 100% efficiency in the ideal case. In this dissertation, a short range wireless power transfer system, based on a Class E power converter, is investigated. It operates at 200 kHz and was constructed using commonly available components. A mathematical analysis of a Class E RF power amplifier, operating at 3.9 MHz, is then presented. The model is based on modern state-space techniques and is simulated using both MATLAB and Simulink. Class E RF power amplifiers are insensitive to signal amplitude variations so by itself, this system is only suitable for the amplification of constant envelope signals. This limitation can be overcome, however, with the addition of a supply modulator. One of the most efficient supply modulators is the Class G dual supply modulator. This device utilizes two supply voltages and automatically switches between them depending on signal amplitude. The process of switching from one supply voltage to the other produces transients or ”glitches” that introduce undesirable broadband noise into the signal output. The effects of these glitches, on the noise floor at the Class E power amplifier output, are investigated using a detailed simulation model run on MATLAB. A typical input data stream, glitch depth, and glitch duration are applied to this operating model. As a potential design aid, a purely hypothetical Class E amplifier state-space based model is analyzed based on same simplifying assumptions including a truncated Taylor series expansion of the matrix exponential. Two algebraic equations were derived to determine two Class E amplifier design components. Class E systems are often designed using Raab’s formulas which were derived based on a number of simplifying assumptions. Furthermore, electronic components have tolerances. As a consequence of this a Class E amplifier or power converter must be tuned for proper operation. In order to simplify this process a detailed sensitivity analysis of the Class E circuit topology is presented. This investigation is approached from multiple directions including a state-space based model simulated using MATLAB, a SPICE based simulation, and an experimental Class E prototype operating at 100 kHz.Ph.D.Includes bibliographical referencesby Sumati Sehajpa

    Factors influencing roll-out of an m-Health intervention in India: Results from a dynamic and responsive process evaluation

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    Implementation research can support iterative program improvement, yet limited examples of such dynamic experiences exist. We conducted a multi-stage and multi-method process evaluation (PE) of a large-scale m-Health intervention in India that currently reaches 581,282 frontline workers (FLWs). The intervention (Common Application Software (CAS)) includes a smartphone application that digitizes FLW service-tracking registers and acts as a job aid and multiple dashboards for real-time monitoring. We examined factors affecting the roll-out of CAS in two Indian states

    M-Health intervention has the potential to alleviate constraints in using administrative data systems for improving service delivery in India

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    Administrative Data (AD) are a key component of nutrition data systems, but little is known about how AD are used or can be reshaped for accountability and action. We studied factors influencing AD use in India's Integrated Child Development Services (ICDS), in two Indian states; and assessed how an m-Health intervention (Common Application Software (CAS)) changes it. ICDS-AD system consolidates data from 11-recording registers updated every month by ∼1.3 million frontline workers (FLW). CAS digitizes these records and creates dashboards for real-time monitoring

    Protecting Traditional Knowledge Digitally: a Case Study of TKDL

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    Traditional knowledge on biodiversity from India has been particularly vulnerable to patent claims and the Indian government and NGOs have made several biopiracy claims in recent years. India has taken various initiatives regarding the protection of traditional knowledge under intellectual property rights, including the Traditional Knowledge Digital Library (TKDL), which is a major step to curb biopiracy. The paper discusses various aspects of TKDL including its role in the preservation, protection and dissemination of traditional knowledge, searching facilities, benefits, and current status. The paper also tries to explore the Traditional Knowledge Resources Classification

    Routine growth monitoring processes in nutrition programs in India have multiple falter points with implications for quality of care

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    Growth monitoring (GM) and promotion is a routine part of primary healthcare for children in >80% of countries. In India, 57.5 million children are measured every month by frontline workers to assess their growth and to trigger preventive or curative services. Standard guidance for anthropometry suggests that quality can be compromised by the choice of measurement equipment, placement of equipment, and positioning of children during measurement. Little is known about the quality of measurement processes during GM. We compared child height and weight measurement processes with standards for anthropometry to assess GM quality

    Coverage of nutrition and health interventions in Sikkim: Insights from the National Family Health Survey-4

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    This Data Note describes the coverage of a set of key nutrition and health interventions. The findings here are based on data from the National Family Health Survey 2015-2016. Indicators to capture the coverage of the interventions here are all calculated for women (15-49 years) with a child under five years of age. All analyses are based on the last-born child for each woman and indicator definitions are provided in Annex 1 of this Note. For some indicators, age categories may vary
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