29 research outputs found

    Impact of DSCSA on United States pharmaceutical industry under decentralized information flow

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    Thesis: M. Eng. in Supply Chain Management, Massachusetts Institute of Technology, Supply Chain Management Program, 2017.Cataloged from PDF version of thesis.Includes bibliographical references (pages 46-47).Drug counterfeiting is one of the major issues in the pharmaceutical industry across the world. These products could cause damages from ineffective treatments to death of patients. In order to fight against counterfeit drugs, the US government introduced Drug Supply Chain Security Act (DSCSA) mandating that all prescription drugs should be serialized. In addition, it mandates all pharmaceutical companies in the U.S. to provide tracking documents in response to a tracing request from FDA. While the act aims to improve drug security across the pharmaceutical industry, it poses a huge impact across the supply chain on both physical flow and information flow. This research evaluates the supply chain impact at an industry level. In this thesis, we evaluate the supply chain impact of Matryoshka model and Unit level model supported by a decentralized information flow. The thesis then evaluates the supply chain impact from three aspects, operational cost, IT infrastructure cost and capital investment. We reference Nabiyeva and Wu's research on centralized information flow model to conduct an exhaustive supply chain impact evaluation across the centralized model and the decentralized model. We conclude that among all these scenarios, unit level model under centralized information flow design bears the highest cost as it requires higher IT investment. On the other hand, the matryoshka model under decentralized information flow has a least supply chain impact from the cost perspective with low IT investment.by Meng Ying Chang and Raghavendran Mohan.M. Eng. in Supply Chain Managemen

    Study of droplet dynamics in transcritical environments

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    Efficient combustion processes are indispensable in limiting the temperature increase to 1.5 deg C as set by Intergovernmental Panel on Climate Change (IPCC) before 2030 to curtail the effects of global warming. As for the emissions, the main task lies in controlling the air-fuel ratio in the lean regime as to control the emissions of NOx since they reach maximum discharge at the stoichiometric ratio whereas improper mixing can lead to an increase in CO emissions. Thus, the air and fuel interactions need to be studied to achieve control over emissions. To that end, good computational models are necessary to supplement the design process to control both the emissions and combustion instabilities. The latter can severely damage the combustion chamber. Therefore, the proper modeling of the fuel-air interfaces in high-pressures is pivotal as they differ significantly from the low-pressure injection. Various numerical droplet evaporation models are studied in trans/supercritical environments, the fluid is called supercritical when it's above the critical states whereas it is called transcritical when it passes the critical state. As for the droplets, two components were selected namely n-heptane and n-dodecane. The former for 0-D and 1-D models and the latter for 3-D models, the cases were dictated by the availability of experimental works. As for the 0-D and 1-D models, various correlations based on the Nusselt and Sherwood numbers were utilized. The Prandtl number and other non-dimensional numbers were computed by thermophysical property models based on the 1/3 rd rule rather than fixed values. In comparison, the developed 0-D and 1-D models conform to the experimental results and other computational studies ranging from perfect-gas to real-gas against the experimental work available in the literature. It is hypothesized that the differences in the computation of the latent heat of vaporization are more pronounced in the accuracy of the lifetime of the droplet rather than the density of the components. In 3-D models, the liquid-vapor interface is modeled by level-set and phase-field methods. Thermodynamic closure is achieved by the Peng- Robinson equation of state. Prandtl number assumption model is invoked for the computation of the liquid thermal conductivity, Chung model for the calculation of viscosity of mixtures, and Firoozabadi model for the Maxwell-Stefan diffusion coefficient. A basic model is used for the computation of surface tension coefficient for the phase-field 3-D models. A qualitative agreement was observed between the 3D model under this study, numerical work, and the experimental campaign of microscopic droplets for all the three vaporization regimes namely classical, translational and diffusive mixing. All the models yielded olive-shaped droplets. Effects of mesh resolution on the phase-field quantities were studied and contrasted with the same mesh size for the level set method in a 2-D configuration. Recommendations include better surface tension models, thermal conductivity for gaseous mixtures, the inclusion of PC-SAFT equation of state, cross-diffusion terms, and high mesh resolution of the O(-7) m in the droplet region coupled with adaptive meshing based on the gradient of the phase-field parameter.Aerospace Engineerin

    Urinary Bladder Xanthoma – Is Immunohistochemistry Necessary?

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    AbstractUrinary Bladder Xanthomas (UBX) are non-neoplastic reactive tumor like process. Isolated UBX is rare with only around 15 cases reported (Yu, Patel, & Bonert, 2015). UBX are reported in older patients who present with non specific symptoms like UTI or hematuria. Patients often have associated lipid anomalies. UBX have been vaguely described as yellowish white plaques or patches. Also, recent reports have stressed on the role of Immunohistochemistry in the diagnosis (Al-Daraji, Varghese, & Husain, 2007; Vimal, Masih, Manipadam, & Chacko, 2012). The objective of this report is to provide a cystoscopic view of the tumor which will enable easier identification and also to debate on the role of IHC in diagnosis

    Enhanced Laterally Resolved ToF-SIMS and AFM Imaging of the Electrically Conductive Structures in Cable Bacteria

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    Cable bacteria are electroactive bacteria that form a long, linear chain of ridged cylindrical cells. These filamentous bacteria conduct centimeter-scale long-range electron transport through parallel, interconnected conductive pathways of which the detailed chemical and electrical properties are still unclear. Here, we combine time-of-flight secondary-ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM) to investigate the structure and composition of this naturally occurring electrical network. The enhanced lateral resolution achieved allows differentiation between the cell body and the cell-cell junctions that contain a conspicuous cartwheel structure. Three ToF-SIMS modes were compared in the study of so-called fiber sheaths (i.e., the cell material that remains after the removal of cytoplasm and membranes, and which embeds the electrical network). Among these, fast imaging delayed extraction (FI-DE) was found to balance lateral and mass resolution, thus yielding the following multiple benefits in the study of structure-composition relations in cable bacteria: (i) it enables the separate study of the cell body and cell-cell junctions; (ii) by combining FI-DE with in situ AFM, the depth of Ni-containing protein - key in the electrical transport - is determined with greater precision; and (iii) this combination prevents contamination, which is possible when using an ex situ AFM. Our results imply that the interconnects in extracted fiber sheaths are either damaged during extraction, or that their composition is different from fibers, or both. From a more general analytical perspective, the proposed methodology of ToF-SIMS in the FI-DE mode combined with in situ AFM holds great promise for studying the chemical structure of other biological systems.BT/Environmental Biotechnolog

    Studies on the Oxidation of As(III) to As(V) by In-Situ-Generated Hypochlorite

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    The objective of this study is to oxidize arsenite, which is denoted as As(III), into arsenate, which is denoted as As(V), with an in-situ-generated hypochlorite, using metal-oxide-coated titanium and stainless steel as the insoluble anode and cathode, respectively. The cells were operated at different pH values (pH 3-8), temperatures (300-333 K), concentrations of chloride (50-500 mg/L), and current densities (0.02-0.22 mA/dm2). The oxidation of As(III) (3 mg/L) to As(V) with in-situ-generated hypochlorite proceeds efficiently (by achieving a oxidation efficiency of 100%) when 125 mg/L of chloride (pH 7.00) is electrolyzed at a current density of 0.04 mA/dm2 and a temperature of 300 K. It is proven that oxidation by electrolytically formed hypochlorite is a more convenient method/process than dosing the solution with other oxidants

    SOME PROJECTIVE DISTANCE INEQUALITIES FOR SIMPLICES IN COMPLEX PROJECTIVE SPACE

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    Abstract. We prove inequalities relating the absolute value of the determi-nant of n + 1 linearly independent unit vectors in Cn+1 and the projective distances from the vertices to the hyperplanes containing the opposite faces of the simplices in complex projective n-space whose vertices or faces are deter-mined by the given vectors. A basis of unit vectors in Cn+1 determines the vertices (or the faces) of a simplex in n-dimensional complex projective space. For reasons originally motivated by an inequality in complex function theory proven by Eremenko and the third author [CE], we investigated the relationship between the determinant of the vectors form-ing the basis and the projective distances from each vertex of the simplex to the hyperplane containing the face of the opposite side. We show that if dmin denotes the minimum of these projective distances and if D denotes the determinant of the basis vectors, then dnmin ≤ |D | ≤ dmin. Acknowledgments. Surya Raghavendran, during a research experiences for un-dergraduates project supervised by the third author and funded by a SUMS fel

    Efficient long-range conduction in cable bacteria through nickel protein wires

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    Filamentous cable bacteria display long-range electron transport, generating electrical currents over centimeter distances through a highly ordered network of fibers embedded in their cell envelope. The conductivity of these periplasmic wires is exceptionally high for a biological material, but their chemical structure and underlying electron transport mechanism remain unresolved. Here, we combine high-resolution microscopy, spectroscopy, and chemical imaging on individual cable bacterium filaments to demonstrate that the periplasmic wires consist of a conductive protein core surrounded by an insulating protein shell layer. The core proteins contain a sulfur-ligated nickel cofactor, and conductivity decreases when nickel is oxidized or selectively removed. The involvement of nickel as the active metal in biological conduction is remarkable, and suggests a hitherto unknown form of electron transport that enables efficient conduction in centimeter-long protein structures.</p

    Osteogenic differentiation of mesenchymal stem cells on a poly (octanediol citrate)/bioglass composite scaffold in vitro

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    This study investigated the effect of composite scaffolds composed of poly (octanediol citrate) (POC) and a bioactive glass (composition, 48%SiO2-12%CaO-32%ZnO-8%Ga2O3) on the growth and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). All the scaffolds, regardless of the amount of bioglass incorporation, were able to support the growth of hBMSCs and guide their osteogenic differentiation without osteogenic media stimulation. The expression of bone-associated genes (runt-related transcription factor 2, type I collagen, bone morphogenetic protein 2, osteonectin and osteocalcin) was significantly increased by a culture time of up to 2 weeks, particularly for the composite scaffold loaded with 10% bioactive glass. The composite scaffolds significantly stimulated alkaline phosphatase (ALP) activity compared to the pure POC scaffold. Cellular mineralization of the secreted extracellular matrix illustrated a higher calcium level on the composites than on the pure POC and increased with culture time. These results suggest that composite scaffolds of POC and a bioactive glass can provide favourable conditions for osteogenic differentiation of hBMSCs and can potentially be used to induce bone healing and regeneration

    Potential Use of 3D CORAGRAF-Loaded PDGF-BB in PLGA Microsphere Seeded Mesenchymal Stromal Cells in Enhancing the Repair of Calvaria Critical-Size Bone Defect in Rat Model

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    Our previous study evidenced that the 3D CORAGRAF loaded with PLGA microsphere constitutes PDGF-BB can support cell attachment and proliferation and can induce an osteogenic commitment of mesenchymal stromal cells in the in vitro condition. However, how this construct can perform in pathophysiological conditions in terms of repairing critical bone defects is yet to be understood. A study was therefore conducted to investigate the regeneration potential of calvaria critical-size defects using CORAGRAF + PLGA with PDGF-BB + mesenchymal stromal cells (MSCs) in a rat model. A 5 mm critical bone defect was created on calvaria of 40 male Sprague-Dawley rats. CORAGRAF incorporated either with or without PDGF-BB and seeded with rat bone-marrow-derived MSCs was implanted at the defect region. The bone regeneration potential of implanted constructs was assessed using micro-CT imaging and histological staining in weeks 4 and 8. The micro-CT images indicated a significant closure of defects in the cranial bone of the rats treated with 3D CORAGRAF + PLGA with PDGF-BB + MSCs on week 4 and 8 post-implantation. This finding, further supported with the histology outcome where the rat cranial defect treated with CORAGRAF + PLGA with PDGF-BB + MSCs indicated neo-bony ingrowth with organized and mature bone-like morphology as compared with other groups. The previous in vitro results substantiated with our pre-clinical findings demonstrate that the combination of CORAGRAF + PLGA with PDGF-BB + MSCs could be an ideal construct to support bone regeneration in critical bone defects. Hence, this construct can be further investigated for its safety and efficacy in large animal models, or it can be skipped to human trial prior for commercialization
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