A Comparative Study of the Strategies Employed in "The Old Man and the Sea" Translated from English into Persian on the Basis of Vinay and Darbelnet's Model

Translation as a culture-based phenomenon has been investigated from various perspectives and it is a field of knowledge that is wide open and has not been exhausted yet. The aim of this study is to examine the use of Vinay and Darbelnet’s translation strategies in translation of the novel “The Old Man and the Sea” from English to Persian by Najaf Daryabandari and Mohammad Taghi Faramarzi.  It also made an attempt to investigate which of the two main categories of translation strategies (direct and oblique translation) is the prevalent tendency in translation of this novel by the two translators

Before the Storm: Youth Hockey in North Carolina Ahead of the NHL’s Arrival

This thesis looks at the development of youth hockey in North Carolina before the coming of the National Hockey League’s Carolina Hurricanes in 1997. Although the American South with its warm weather and lack of snow or ice seemed inhospitable to such a wintry sport, ice hockey found a niche in Charlotte, the Piedmont Triad, and the Research Triangle in the mid- to late- 20th century through a combination of minor professional teams, local boosters, and northern transplants who all worked together to organize youth and amateur hockey associations as well as advocate for accessible ice rink facilities in order to grow the game. As a microcosm of the New South and postwar America, the story of North Carolina hockey reflects larger homogenization and migration trends across state and regional borders in this time period. Moreover, while minor professional hockey sparked a lifelong love for the game, participation in youth hockey produced long-lasting communities and shaped North Carolina hockey into a viable major league marke

Reconstructing Article 109(3) of the UN Charter: Towards Constitutionalisation of the United Nations and International Law

ABSTRACT By critically assessing the discourse, intent and teleology of the United Nations Charter when the text of the instrument was being finalised in 1945, this thesis argues that the majority of the world's states gathered at the UN Conference on International Organisation in San Francisco were aware of the fact that the core provisions of the treaty were being dictated by the five permanent members of the Security Council. Nevertheless, these states accepted the Charter in its current form in return for the promise of a more democratic UN in the future. This qualified acceptance was manifested in Article 109 of the Charter and, more specifically, in that article's paragraph 3, which provided for a facilitated Charter review in ten years' time. Recognising that globalisation has outpaced fragmented state-centric global governance, and that world-wide threats in areas such as the violation of human rights, climate change, armed conflicts, and the use of conventional and nuclear weapons continue to exist, this thesis argues that elusive global governance and its instrument of international law are, in the absence of a global government, ill-equipped to deal effectively with these borderless problems. Bridging the governmental gap, however, the UN Security Council, with its monopoly on the use of force in order to maintain "peace and security" under Chapter VII of the Charter, has demonstrated erratic and unplanned competencies. In fact, in the past 25 years, the Council has deployed its auto-interpreted expanded powers in the diverse areas of court-making, law-making, defining criminality and sanctioning non-state actors as criminals. It has even involved itself in the settlement of tort claims, awarding damages to individuals and corporations. The Council has, in effect, emerged at the apex of the legal order and has shown its capacity to legislate globally. The founders, when drafting the Charter, were aware of the democratic and legitimacy deficiencies of the Council and, in order to redress them, and to apply the experiences learned during the UN's first years of operation, provided for a revisions process, including the holding of a Charter review conference, as enshrined in Article 109. Why the UN has never in its 70-year history held such a review conference, and whether paragraph 3 of Article 109-neglected by researchers and politicians-is still in force, are at the core of this thesis's analysis. It will be argued that, if such a review conference is convened now, it would most likely trigger the process of UN constitutionalisation, and thus help transform the UN, so it can ultimately fulfil the objectives set out in the Charter's preamble-including guaranteeing and the protecting the fundamental rights of "we the peoples"

Vector-free microfluidic platform for intracellular delivery of macromolecules

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2013."June 2016." Cataloged from PDF version of thesis.Includes bibliographical references (p. 158-165).Intracellular delivery of material is a long-standing challenge for both therapeutic and research applications. Existing technologies rely on a variety of mechanisms to facilitate delivery. Vector-based methods, such as polymeric nanoparticles and liposomes, form complexes with the target material and subsequently facilitate its uptake by the cell of interest, often through endocytosis. Although effective in some applications, these methods have had difficulty translating to patient-derived primary cells, especially stem cells and immune cells. Moreover, these vectors are often limited in the range of target materials they can deliver and leave much material trapped in endocytotic vesicles. Physical methods, such as electroporation and sonoporation, have been able to address some of the challenges with vector-based methods by providing a platform for physical disruption of the cell membrane. By eliminating the need for vector materials and circumventing the endocytotic pathway, these methods have shown an advantage in some applications, especially those involving primary cells that are recalcitrant to vector-based methods. However, both electroporation and sonoporation suffer from high cell toxicity and have had limited success in delivering materials such as proteins and nanomaterials. Electroporation in particular has been shown to damage certain target materials, such as quantum dots. Microinjection, an alternative method in which cells are punctured by a microneedle, can address a variety of target materials and cell types however its low throughput has hindered its adoption for most applications. There is thus a need for more effective intracellular delivery methods. This dissertation describes a microfluidic approach to intracellular delivery that seeks to embody the advantages of a physical method, while mitigating issues related to toxicity and damage to the target material. In our method, the cells of interest are prepared in suspension with the target delivery material and flown through a parallel network of microfluidic channels. Each channel contains a constriction point where the cells are rapidly deformed, or squeezed, as they pass through. This process induces temporary disruption of the cell membrane thereby enabling diffusive transport of material from the surrounding buffer into the cell cytosol. These disruptions persist for less than 5min before membrane integrity is fully restored. This method has thus far been demonstrated in over 15 cell types and has been able to deliver a variety of functional materials including, DNA, RNA, proteins, quantum dots, carbon nanotubes, and small molecules. Our cell squeezing technology has further illustrated its enabling potential in a number of applications detailed herein. Quantum dots are a promising alternative to organic fluorescent dyes due to their superior spectral properties and stability. These nanoparticles have much potential as imaging agents in vitro and in vivo. Delivery of undamaged quantum dots to the cell cytoplasm has been a challenge with existing techniques. Vector-based methods have resulted in aggregation and endosomal sequestration of quantum dots while electroporation can damage the semi-conducting particles and aggregate delivered dots in the cytosol. In our work, we demonstrated efficient cytosolic delivery of quantum dots without inducing aggregation, trapping material in endosomes, or significant loss of cell viability. Moreover, we have shown that individual quantum dots delivered by this approach are detectable in the cell cytosol, thus illustrating the potential of this technique for single molecule tracking studies. These results indicate that our method could potentially be implemented as a robust platform for quantum dot based imaging in a variety of applications. The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has much potential in its ability to address existing challenges in regenerative medicine by providing a patient-specific source of pluripotent stem cells to generate new tissue. The mechanism of this reprogramming process, however, is still poorly understood and existing technologies suffer from chronically low reprogramming efficiencies (<4%). Moreover, many existing approaches to reprogramming rely on viral vectors to facilitate the delivery of the target transcription factors - these vectors are considered inappropriate for clinical applications due to safety concerns. Cytosolic delivery of protein transcription factors is a possible alternative to viral and plasmidbased reprogramming techniques. Direct protein delivery would negate the current safety concerns with viral and plasmid-based methods as it could not cause potentially tumorigenic changes in the genome. In our work, we implemented the cell squeezing technology as a method to deliver protein transcription factors to the cytosol of primary human fibroblasts. These studies yielded colonies of pluripotent stem cells that appeared to be fully functional. Moreover, the efficiency of this procedure was 10-100x higher than the current state-of-the-art protein reprogramming methods. The versatility of our delivery technology thus provides a promising platform for further study of the reprogramming process and the development of more efficient, clinically applicable, reprogramming procedures. Finally, the technology described herein has been implemented in cancer vaccine applications. Some recent immunotherapies against cancer have focused on the use of dendritic cells as antigen presenting cells. These cells are capable of presenting cancer antigens to other immune cell subsets and prompting a powerful immune response against the target cell type. A significant challenge for these therapies, however, is that current methods to induce antigen presentation in dendritic cells are often inefficient and can potentially induce a parallel regulatory response that reduces treatment efficacy. In our work, we have implemented the device as a platform for direct cytosolic delivery of the target antigen to dendritic cells. This approach could enable effective presentation of the target antigen while minimizing the development of a regulatory response. Our results indicate that this approach can produce effective antigen presentation in vitro, as measured by CD8 T cell coculture assays. Moreover, we have demonstrated effective antigen presentation in B cells, a more desirable clinical alternative to dendritic cells. These results thus illustrate the potential of this technology to be implemented as an enabling, patient-specific vaccination platform with minimal side-effects. In summary, we have developed a robust, high-throughput approach to intracellular delivery. In the described technique, cytosolic delivery is facilitated by the temporary disruption of the cell membrane in response to rapid mechanical deformation of the cell in a microfluidic channel. This technology seeks to addresses some of the challenges of existing vector-based and physical poration methods, such as endocytosis, translation to primary cells, and cell toxicity. Our results in quantum dot, cell reprogramming, and cancer vaccine applications illustrate the strengths of this system. Although in its infancy, this technology has demonstrated the potential to enable a range of clinical and research applications. In the future, better understanding of the underlying mechanism and improvements to the system could produce substantial gains in performance and allow this technique to be widely adopted by researchers and clinicians.by Armon R. Sharei.Ph.D

In vitro and ex vivo strategies for intracellular delivery

Intracellular delivery of materials has become a critical component of genome-editing approaches, ex vivo cell-based therapies, and a diversity of fundamental research applications. Limitations of current technologies motivate development of next-generation systems that can deliver a broad variety of cargo to diverse cell types. Here we review in vitro and ex vivo intracellular delivery approaches with a focus on mechanisms, challenges and opportunities. In particular, we emphasize membrane-disruption-based delivery methods and the transformative role of nanotechnology, microfluidics and laboratory-on-chip technology in advancing the field.National Institutes of Health (U.S.) (R01GM101420-01A1

Microfluidic jet injection for delivering macromolecules into cells

We present a microfluidic-based injection system designed to achieve intracellular delivery of macromolecules by directing a picoliter jet of a solution toward the individual cells. After discussing the concept, we present design specification and criteria, elucidate performance and discuss results. The method has the potential to be quantitative and of high throughput, overcoming the limitations of current intracellular delivery protocols.Deshpande Center for Technological InnovationNational Institutes of Health (U.S.) (Grant RC1 EB011187-02

Live-cell protein labelling with nanometre precision by cell squeezing

Live-cell labelling techniques to visualize proteins with minimal disturbance are important; however, the currently available methods are limited in their labelling efficiency, specificity and cell permeability. We describe high-throughput protein labelling facilitated by minimalistic probes delivered to mammalian cells by microfluidic cell squeezing. High-affinity and target-specific tracing of proteins in various subcellular compartments is demonstrated, culminating in photoinduced labelling within live cells. Both the fine-tuned delivery of subnanomolar concentrations and the minimal size of the probe allow for live-cell super-resolution imaging with very low background and nanometre precision. This method is fast in probe delivery (~1,000,000 cells per second), versatile across cell types and can be readily transferred to a multitude of proteins. Moreover, the technique succeeds in combination with well-established methods to gain multiplexed labelling and has demonstrated potential to precisely trace target proteins, in live mammalian cells, by super-resolution microscopy

Shear Strength Prediction of Reinforced Concrete Shear Wall Using ANN, GMDH-NN and GEP

To provide lateral resistance in structures as well as buildings, there are some types of structural systems such as shear walls. The utilization of lateral loads occurs on a plate on the wall's vertical dimension. Conventionally, these sorts of loads are transferred to the wall collectors. There is a significant resistance between concrete shear walls and lateral seismic loading. To guarantee the building's seismic security, the shear strength of the walls has to be prognosticated by using models. This paper aims to predict shear strength by using Artificial Neural Network (ANN), Neural Network-Based Group Method of Data Handling (GMDH-NN), and Gene Expression Programming (GEP). The concrete's compressive strength, the yield strength of transverse reinforcement, the yield strength of vertical reinforcement, the axial load, the aspect ratio of the dimensions, the wall length, the thickness of the reinforced concrete shear wall, the transverse reinforcement ratio, and the vertical reinforcement ratio are the input parameters for the neural network model. And the shear strength of the reinforced concrete shear wall is considered as the target parameter of the ANN model. The results validate the capability of the models predicted by ANN, GMDH-NN, and GEP, which are suitable for use as a tool for predicting the shear strength of concrete shear walls with high accuracy

Plasma membrane recovery kinetics of a microfluidic intracellular delivery platform

Intracellular delivery of materials is a challenge in research and therapeutic applications. Physical methods of plasma membrane disruption have recently emerged as an approach to facilitate the delivery of a variety of macromolecules to a range of cell types. We use the microfluidic CellSqueeze delivery platform to examine the kinetics of plasma membrane recovery after disruption and its dependence on the calcium content of the surrounding buffer (recovery time ~5 min without calcium vs. ~30 s with calcium). Moreover, we illustrate that manipulation of the membrane repair kinetics can yield up to 5× improvement in delivery efficiency without significantly impacting cell viability. Membrane repair characteristics initially observed in HeLa cells are shown to translate to primary naïve murine T cells. Subsequent manipulation of membrane repair kinetics also enables the delivery of larger materials, such as antibodies, to these difficult to manipulate cells. This work provides insight into the membrane repair process in response to mechanical delivery and could potentially enable the development of improved delivery methods.National Institutes of Health (U.S.) (Grant RC1 EB011187-02)National Institutes of Health (U.S.) (Grant R01GN101420-01A1)Kathy and Curt Marble Cancer Research FundNational Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant MPP-09Call-Langer-60

Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines

B-cells are promising candidate autologous antigen-presenting cells (APCs) to prime antigen-specific T-cells both in vitro and in vivo. However to date, a significant barrier to utilizing B-cells as APCs is their low capacity for non-specific antigen uptake compared to “professional” APCs such as dendritic cells. Here we utilize a microfluidic device that employs many parallel channels to pass single cells through narrow constrictions in high throughput. This microscale “cell squeezing” process creates transient pores in the plasma membrane, enabling intracellular delivery of whole proteins from the surrounding medium into B-cells via mechano-poration. We demonstrate that both resting and activated B-cells process and present antigens delivered via mechano-poration exclusively to antigen-specific CD8[superscript +]T-cells, and not CD4[superscript +]T-cells. Squeezed B-cells primed and expanded large numbers of effector CD8[superscript +]T-cells in vitro that produced effector cytokines critical to cytolytic function, including granzyme B and interferon-γ. Finally, antigen-loaded B-cells were also able to prime antigen-specific CD8[superscript +]T-cells in vivo when adoptively transferred into mice. Altogether, these data demonstrate crucial proof-of-concept for mechano-poration as an enabling technology for B-cell antigen loading, priming of antigen-specific CD8[superscript +]T-cells, and decoupling of antigen uptake from B-cell activation.Kathy and Curt Marble Cancer Research Fund (Frontier Research Programme Grant)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F32CA180586