3,774 research outputs found
Multicomponent targeted proapoptotic anticancer drug delivery system
No full textCancer is one of the leading causes of death in United States. The current approaches for the treatment of solid tumor available are the surgery for the removal of primary tumor followed by chemotherapy and /or radiation. The efficacy of chemotherapy is limited by the following factors; (1) adverse side-effects on healthy organs, (2) development of cellular resistance and (3) low solubility of many anticancer drugs. The primary objective of this dissertation is to overcome all the above stated limitations. The methods employed in this dissertation includes designing, synthesizing and evaluating a novel drug delivery system comprising of 1) multiple copies of an anticancer drug, Camptothecin (CPT) ; 2) a polymeric carrier, Polyethylene glycol (PEG); 3) multiple copies of a targeting moiety to cancer cells, Luteinizing hormone releasing hormone (LHRH) peptide; 4) multiple copies of a suppressor of antiapoptotic cellular defense, BH3 peptide both in vitro and in vivo on A2780 human ovarian carcinoma cells and malignant ascites and animal models respectively. Conjugates of CPT, LHRH and CPT, LHRH, BH3 were evaluated for cytotoxicity, cancer specificity and antitumor activity. The multicomponent anticancer delivery system will significantly enhance the efficacy of an anticancer drug in the treatment of all the stages of cancer when compared with free drug, non-targeted delivery systems or the system consisting of one copy of each active component.Ph.D.Includes bibliographical referencesIncludes vitaby Pooja Chandn
Offshoring and outsourcing of core corporate activities: the global relocation of pharmaceutical industry clinical trials
No full textThis dissertation examines the offshoring and outsourcing of core activities in the pharmaceutical industry. Using primary and secondary data sources, the dissertation adopts a multi-level approach to examine four research questions related to the sourcing strategies of core activities such as clinical trials. Specifically, I look at operational and strategic factors that influence the decision to relocate core activities both organizationally (in-house versus external vendors) and geographically (activities conducted in home nation versus trials in foreign countries). Drawing on Dunning's framework, the dissertation next examines the role of four motives (resource, market, efficiency and strategic asset seeking) in the offshoring decisions while distinguishing between offshore outsourcing and offshoring to foreign affiliates. Using multiple case studies, the third study further investigates the evolution of firms sourcing strategies from conducting core activities in-house to increasingly outsourcing and offshoring them. The final study in the dissertation examines the impact of offshoring and outsourcing on the performance of core activities. Data for this dissertation comes from multiple sources: Primary data from in-depth structured interviews and online survey of vice presidents of clinical affairs of pharmaceutical and biotechnology firms, as well as secondary data from Medidata, Orbis, and World Development Indicators. The dissertation offers evidence that firms tend to use different sourcing strategies for different motives. Specifically, offshoring to foreign affiliates is primarily driven by strategic factors and firms tend to prefer this strategy for strategic asset seeking purposes. Offshore outsourcing on the other hand is motivated by resource and efficiency seeking behavior and the important determinants for this strategy are mainly operational. The third type of sourcing strategy is domestic outsourcing and firms are driven by both strategic as well as operational determinants for this strategy. The qualitative study on strategy evolution points towards a five stage process which begins with in-house sourcing followed by domestic outsourcing, foreign affiliates, offshore outsourcing and finally backsourcing of core activities. Evidence from the dissertation suggests that outsourcing has a positive impact on performance when compared to in-house while offshoring has a negative impact compared to domestic sourcing.Ph.D.Includes abstractVitaIncludes bibliographical referencesby Pooja Thaku
Powerful Teaching: Unleash the Science of Learning
No full textLibrarian, Judy Pinnolis, discusses Powerful Teaching: Unleash the Science of Learning by Dr. Pooja K. Agarwal, Assistant Professor at Berklee College of Music, and Patrice M. Bain.
Video editing by Stacey Snyder.https://remix.berklee.edu/library-books-at-berklee/1001/thumbnail.jp
The Brylinski beta function of a coaxial layer
Get PDFIn [Pooja Rani and M. K. Vemuri, The Brylinski beta function of a double layer, Differential Geom. Appl. \textbf{92}(2024)], an analogue of Brylinski\u27s knot beta function was defined for a compactly supported (Schwartz) distribution on Euclidean space. Here we consider the Brylinski beta function of the distribution defined by a coaxial layer on a submanifold of Euclidean space. We prove that it has an analytic continuation to the whole complex plane as a meromorphic function with only simple poles, and in the case of a coaxial layer on a space curves, we compute some of the residues in terms of the curvature and torsion
Dynamic Planning for Flexible Port Infrastructure after Panama Canal Expansion: A Real Case Study
No full textThis paper presents a study carried out to first assess the impact of the Panama Canal expansion (PCE) on selected Caribbean ports, and thereafter, to examine how the ports can adapt in order to seize new opportunities created by the expansion. An applied case of long-term dynamic planning and flexibility in engineering design is presented for a new port terminal in Barranquilla, Colombia. Furthermore, this paper presents the results of a stochastic method for quantifying opportunities from containerized traffic using dynamic forecasting, real options analysis, and Monte Carlo simulation, within the framework and spirit of adaptive port planning under uncertainty.Accepted Author ManuscriptRivers, Ports, Waterways and Dredging Engineerin
Design, Synthesis And Evaluation Of Novel Antimycobacterial Compounds Targeting The MmpL3 Transporter Protein.
No full textTuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (M. tb). TB is one of the leading causes of death in developing countries. Current TB therapy requires a minimum six-month treatment and is associated with increasing drug resistance and decreased patient compliance. Therefore, new anti-TB compounds with novel mechanisms of action that have activity against resistant strains and can potentially reduce treatment duration are urgently needed. Mycolic acids are the primary lipid components in the mycobacterial cell wall and are responsible for mycobacterial cell wall integrity, permeability and virulence. Mycobacterial membrane protein large 3 (MmpL3) is an essential transporter responsible for the translocation of mycolic acids to the outer membrane. Published indole-2-carboxamides with suggested MmpL3 inhibition showed good potency, against whole-cell M. tb, yet had poor aqueous solubility. This project hypothesizes that bioisosteric replacement of the indole ring, will maintain anti-tubercular activity with improved aqueous solubility leading to enhanced pharmacokinetics. The project focuses on retaining the required pharmacophore and increasing the molecular heteroatom percentage by reducing lipophilic atoms. The designed and synthesized indole bioisosteres are pyrrole, mandelic acid and imidazole, coupled to lipophilic head groups ensuring anti-tubercular activity. In addition to minimum inhibitory concentration (MIC) determination, the active compounds were subjected to in vitro ADMET assays, including aqueous solubility, permeability and metabolic stability toward mouse liver S9 fractions, to determine their suitability for further in vivo preclinical evaluation.|Lead compounds had improved pharmacokinetics over their indole-2-carboxamide analogs while their potency against mycobacteria varied. It was observed that an improvement in the aqueous solubility negatively impacted the anti-tubercular potency. Pyrrole analogs were found to be the best with respect to activity and had an improved solubility, permeability and were metabolically stable.ProQuest Traditional Publishing Optio
PoojaMiddha/GeRI_colitis: Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis
No full text<p>This repository provides code for developing and validating a polygenic risk score for ulcerative colitis and Crohn's disease and evaluating the role of the polygenic risk score on immune checkpoint inhibitor-mediated colitis, as described in:</p>
<p><strong>Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis</strong></p>
<p>Pooja Middha, Rohit Thummalapalli, Michael J. Betti, Lydia Yao, Zoe Quandt, Karmugi Balaratnam, Cosmin A. Bejan, Eduardo Cardenas, Christina J. Falcon, David M. Faleck, Princess Margaret Lung Group, Matthew A. Gubens, Scott Huntsman, Douglas B. Johnson, Linda Kachuri, Khaleeq Khan, Min Li, Christine M. Lovly, Megan H. Murray, Devalben Patel, Kristin Werking, Yaomin Xu, Luna Jia Zhan, Justin M. Balko, Geoffrey Liu, Melinda C. Aldrich, Adam J. Schoenfeld, Elad Ziv</p>
<p>medRxiv 2023.05.15.23289680; doi: https://www.medrxiv.org/content/10.1101/2023.05.15.23289680v2</p>
Target reliability indices for quay walls, jetties, and flexible dolphins
No full textStructural codes rely on generalised target reliability indices, which are mainly derived for buildings. It is unclear, however, whether these indices are applicable to the specific risk-profile of quay walls, jetties, and flexible dolphins. In this study, target reliability indices for marine structures were derived from various risk acceptance criteria, such as economic optimisation, individual risk, societal risk, the life quality index, and the social and environmental repercussion index. This article uses a method to determine reliability targets distinguishing time-dependent and time-independent variables, because some important stochastic design variables in the design of marine structures, such as soil and material properties, are largely time-independent. The assessment framework of ISO 2394, taking into account social, economic, and environmental impact, has proven to be a solid basis for reliability differentiation. The method of approach considered in this paper can also be used for evaluating target reliability indices of other geotechnical structures.Accepted Author ManuscriptHydraulic Structures and Flood Ris
Bolus Texture Testing as a Clinical Method for Evaluating Food Oral Processing and Choking Risk: A Pilot Study
No full textPurpose: Choking on food is a leading cause of accidental death in several populations, including children, people with intellectual/developmental disability, and older adults in residential care facilities. One contributor to choking risk is incomplete oral processing and failure to convert food to a cohesive, nonsticky bolus with a maximum particle size that will not block the airway. Clinical tests of mastication do not evaluate properties of chewed food boluses. We characterized expectorated boluses, after oral processing, using methods developed by the International Dysphagia Diet Standardisation Initiative (IDDSI). Method: Seventeen adults without dysphagia (seven women and 10 men), aged 23-55 years, chewed samples of a cracker, a raw baby carrot, and a circular, dome-shaped gummy candy. Chewing metrics were obtained up to the point when the person indicated that they were ready to swallow. The bolus was then either expectorated or swallowed; IDDSI tests were used to characterize the expectorated boluses. Results: Measures of chewing did not differ between spit and swallow conditions. Expectorated cracker and carrot boluses had maximum particle size consistent with IDDSI Level SB6 Soft & Bite-Sized foods or lower. The gummy candy samples remained at IDDSI Level RG7 Regular food consistency. Conclusions: This study suggests that expectorated ready-to-swallow boluses are representative of boluses that are swallowed and that oral processing in adults without dysphagia typically results in boluses at IDDSI's Level SB6 or lower. IDDSI's testing methods provide a practical method for evaluating oral processing by characterizing expectorated ready-to-swallow boluses and may guide food texture recommendations for persons who have increased risk of choking
- …
