10 research outputs found
Interplay of polymer and oligonucleotide properties in the nature of antisense effects
No full textAntisense 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
No full textFrom 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
Assessment of knowledge of mothers from migrant population regarding use of oral rehydration solution in diarrheal illness in under-five children from rural Pune
No full textBackground: Diarrhea is one of the important causes of morbidity and mortality among under-five children in India. Lack of knowledge of mothers about the management of diarrheal diseases is a common problem in many developing countries. Use of oral rehydration solution (ORS) largely depends, on the level of mother’s knowledge. Objective: The objective of the study was to assess the knowledge of the mothers, from rural migrant population regarding the use of ORS in under-five children with diarrhea. Materials and Methods: A cross-sectional study was carried out from December 2016 to March 2017, among mothers of the migrant population residing and working at brick kilns and construction site in the field practice area of the rural health training center, Lavale, Pune. We included the mothers whose children were under five years of age. Those mothers, who had serious illness and had hearing and speech problems, were excluded from the study. Data were collected by interview method from mothers with the help of a pre-structured and pre-tested questionnaire. Results: A total of 54 (93.1%) mothers from brick kiln sites were included among whom, 43.10% were aware of ORS. Only 37.93% of mothers knew the use of homemade sugar salt solution for diarrhea in children. In this study, 25 (43.10%) mothers were illiterate and the study showed that knowledge regarding ORS was lower in illiterate mothers. Conclusion: Majority of the mothers were not aware regarding ORS, and as per the study, knowledge regarding ORS was lower in less educated mothers. Government schemes would help these mothers to increase the awareness which will result in a decrease in mortality rate
Design and analysis of class E RF power amplifiers
No full textThe 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
Protecting Traditional Knowledge Digitally: a Case Study of TKDL
No full textTraditional 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
Predictive Model for Construction Labour Productivity Using Hybrid Feature Selection and Principal Component Analysis
No full textConstruction labour productivity (CLP) is affected by numerous variables made up of subjective and objective factors. Thus, CLP modeling and prediction is a complex task, leading to high computational cost and the risk of overfitting of data. This paper proposes a predictive model for CLP by integrating hybrid feature selection (HFS), as a combination of filter and wrapper methods, with principal component analysis (PCA). This developed HFS-PCA method reduces the dimensionality and complexity of CLP data and obtains better prediction performance by identifying the most predictive factors. Identified factors are utilized as inputs for various classification methods to predict CLP. Finally, prediction error of the classification methods with and without using the proposed HFS-PCA method are compared, and the most accurate classification method is selected to develop the CLP predictive model. Experimental results show that using HFS-PCA for CLP prediction leads to better performances compared with past studies.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
Indirect Treatment Comparison of Nivolumab Versus Observation or Ipilimumab as Adjuvant Therapy in Resected Melanoma Using Pooled Clinical Trial Data
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Click-coated, heparinized, decellularized vascular grafts
No full textActa Biomateriala, 13, 177–187Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.A novel method enabling the engineering of a dense and appropriately oriented heparin-containing layer on decellularized aortas has been developed. Amino groups of decellularized aortas were first modified to azido groups using 3-azidobenzoic acid. Azide-clickable dendrons were attached onto the azido groups through "alkyne-azide" click chemistry, affording a tenfold amplification of adhesions sites. Dendron end groups were finally decorated with end-on modified heparin chains. Heparin chains were oriented like heparan sulfate groups on native endothelial cells surface. X-ray photoelectron spectroscopy, nuclear magnetic resonance imaging, mass spectrometry and Fourier transform infrared FTIR spectroscopy were used to characterize the synthesis steps, building the final heparin layered coatings. The continuity of the heparin coating was verified using fluorescent microscopy and histological analysis. The efficacy of heparin linkage was demonstrated with factor Xa anti-thrombogenic assay and platelet adhesion studies. The results suggest that oriented heparin immobilization to decellularized aortas may improve the in vivo blood compatibility of decellularized aortas and vessels.National Institutes of Healt
Glycocalyx‐Like Hydrogel Coatings for Small Diameter Vascular Grafts
No full textAdvanced Functional Matererials, 30, 1908963Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.Novel biological vascular conduits, such as decellularized tissue engineered vascular grafts (TEVGs) are hindered by high thrombogenicity. To mimic the antithrombogenic surface of native vessels with a continuous glycosaminoglycan layer that is present on endothelial cells (ECs), a hyaluronic acid (HA) modified surface is established, to effectively shield blood platelets from collagen-triggered activation. Using the amine groups present on 4 mm diameter decellularized TEVGs, a continuous HA hydrogel coating is built via a bifunctional thiol-reactive cross-linker, thereby avoiding nonspecific collagen matrix cross-linking. The HA hydrogel layer recreates a luminal wall, “hiding” exposed collagen from the bloodstream. In vitro blood tests show that adhered platelets, fibrinogen absorption, and fibrin formation on HA-coated decellularized TEVGs are significantly lower than on uncoated decellularized TEVGs. The HA surface also inhibits macrophage adhesion in vitro. HA-coated decellularized syngeneic rat aortae (≈1.5 mm diameter), and TEVGs in rat and canine models, respectively, are protected from aggressive thrombus formation, and preserve normal blood flow. Re-endothelialization is also observed. HA-coated TEVGs may be an off-the-shelf small-diameter vascular graft with dual benefits: antithrombogenic protection and promotion of endothelium.National Institutes of Healthhttps://login.libproxy.rpi.edu/login?url=https://doi.org/10.1002/adfm.20190896
