Internet goes mobile as billions of users are accessing the Internet through their smartphones. Cellular networks play an essential role in providing “anytime, anywhere” network access as the only large-scale wireless network infrastructure in operation. Mobility support is the salient feature indispensable to ensure seamless Internet connectivity to mobile devices wherever the devices go or are. Cellular network operators deploy a huge number of cell towers over geographical areas each with limited radio coverage. When the device moves out of the radio coverage of its serving cell(s), mobility support is performed to hand over its serving cell(s) to another, thereby ensuring uninterrupted network access.<br>Despite a large success at most places, we uncover that state-of-the-practice mobility support in operational cellular networks suffers from a variety of issues which result in unnecessary performance degradation to mobile devices. In this thesis, we dive into these issues in today’s mobility support and explore possible solutions with no or small changes to the existing network infrastructure.<br>We take a new perspective to study and enhance mobility support. We directly examine, troubleshoot and enhance the underlying procedure of mobility support, instead of higher-layer (application/transport) exploration and optimization in other existing studies. Rather than clean slate network-side solutions, we focus on device-side solutions which are compatible with 3GPP standards and operational network infrastructure, promising immediate benefits without requiring any changes on network side.<br>In particular, we address three technical questions by leveraging the power of the devices. First, how is mobility support performed in reality? We leverage device-side observation to monitor the handoff procedures that happen between the network and the device. We unveil that operator-specific configurations and policies play a decisive role under the standard mechanism and conduct a large-scale measurement study to characterize the extremely complex and diverse handoff configurations used by global operators over the world. Second, what is wrong with the existing mobility support? We conduct model-based reasoning and empirical study to examine network performance issues (e.g., handoff instability and unreachability, missed performance) which are caused by improper handoffs. Finally, how to enhance mobility support? We turn passive devices to proactive devices to enhance mobility support. Specifically, we make a showcase solution which exploits device-side inputs to intervene the default handoff procedure and thus indirectly influence the cell selection decision, thereby improving data speed to mobile devices. All the results in this thesis have been validated or evaluated in reality (over top-tier US carriers like AT&T, Verizon, T-Mobile, some even in global carrier networks).

<p>Adaptation of nucleic acid <em>in vitro</em> selection for whole cell targets has been demonstrated to be an effective means of isolating useful sequences with applications in biomarker detection and therapeutics. The problem of efficient delivery of materials across cell membranes is common to a variety of research and medical fields. Existing aptamers isolated in surfacing binding selections have been successfully adapted for cell targeted therapies through complex modifications. However, better aptamers may be derived from a selection optimized to isolate internalized sequences directly. A cell selection experiment with the goal of identifying circular random-sequence DNA aptamers with the ability to facilitate their own internalization into MCF7 cells was conducted. Several classes of sequences isolated from this selection were shown to target cell nuclei at a rate significantly greater than control sequences as determined by qPCR relative recovery assays supported by <em>in situ</em> RCA fluorescence microscopy data. The localization of functional DNA sequences at the subcellular and intercellular levels suggests a receptor mediated mechanism. Techniques for the selection, purification and fluorescent detection of small circular DNAs were also developed for this study. Further work to characterize and identify targets should be pursued to better understand the mechanism of internalization and judge the suitability of G18d sequences as a delivery platform.</p> / Master of Science (MSc)

abstract: Relapse after tumor dormancy is one of the leading causes of cancer recurrence that ultimately leads to patient mortality. Upon relapse, cancer manifests as metastases that are linked to almost 90% cancer related deaths. Capture of the dormant and relapsed tumor phenotypes in high-throughput will allow for rapid targeted drug discovery, development and validation. Ablation of dormant cancer will not only completely remove the cancer disease, but also will prevent any future recurrence. A novel hydrogel, Amikagel, was developed by crosslinking of aminoglycoside amikacin with a polyethylene glycol crosslinker. Aminoglycosides contain abundant amount of easily conjugable groups such as amino and hydroxyl moieties that were crosslinked to generate the hydrogel. Cancer cells formed 3D spheroidal structures that underwent near complete dormancy on Amikagel high-throughput drug discovery platform. Due to their dormant status, conventional anticancer drugs such as mitoxantrone and docetaxel that target the actively dividing tumor phenotype were found to be ineffective. Hypothesis driven rational drug discovery approaches were used to identify novel pathways that could sensitize dormant cancer cells to death. Strategies were used to further accelerate the dormant cancer cell death to save time required for the therapeutic outcome. Amikagel’s properties were chemo-mechanically tunable and directly impacted the outcome of tumor dormancy or relapse. Exposure of dormant spheroids to weakly stiff and adhesive formulation of Amikagel resulted in significant relapse, mimicking the response to changes in extracellular matrix around dormant tumors. Relapsed cells showed significant differences in their metastatic potential compared to the cells that remained dormant after the induction of relapse. Further, the dissertation discusses the use of Amikagels as novel pDNA binding resins in microbead and monolithic formats for potential use in chromatographic purifications. High abundance of amino groups allowed their utilization as novel anion-exchange pDNA binding resins. This dissertation discusses Amikagel formulations for pDNA binding, metastatic cancer cell separation and novel drug discovery against tumor dormancy and relapse. / Dissertation/Thesis / Doctoral Dissertation Bioengineering 2016

Цель работы – отобрать генотипы растений рода Alissum устойчивые к повышенным концентрациям ионов никеля, меди и цинка. Были выбраны 3 вида растений из рода Alissum sp. семейства Brassicaceae, а именно: A. litvinovii, A. tortuosum, A. оbovatum. В ходе эксперимента из семян были получены растения, которых подвергли микроклональному размножению. Растения культивированы на средах, содержащих Cu2+, Ni2+ или Zn2+ в концентрации 50 – 100 – 200 µМ/л. В течение 6 недель проводили морфологические измерения и описания. После эксперимента было определено содержание ионов Ni2+ в сырой биомассе с использованием реактива Чугаева. Отобраны генотипы растений, устойчивые к избытку тяжелых металлов в среде и способные к активному росту в условиях стресса, генотип A. tortuosum № 6 превысил контроль в 2,6 раза, достигнув размера 46,7 мм (200 µМ Zn2+). Растения показали аккумулирующие способности в отношении ионов никеля в условиях in vitro. Генотип № 5 A. оbovatum аккумулирует 1,59 мг/г Ni2+ сырой массы, что в 8 раз превысило контроль (200 µМ Ni2+). Данное исследование подтверждает перспективность использования растений из рода Alyssum для фиторемедиации. Выпускная квалификационная работа магистра – 61 стр., 21 рис., 5табл., 81 литературных источников, из которых русскоязычных 50, англоязычных 31. / The purpose of the work is to select plant genotypes of the genus Alissum that are resistant to increased concentrations of nickel, copper and zinc ions. Three species of plants from the genus Alissum sp. Brassicaceae family, namely: A. litvinovii, A. tortuosum, A. obovatum. During the experiment, plants were obtained from seeds, which were subjected to microclonal propagation. Plants were cultivated on media containing Cu2+, Ni2+ or Zn2 + at a concentration of 50 – 100 – 200 µM/L. Morphological measurements and descriptions were performed over 6 weeks. After the experiment, the content of Ni2+ ions in the raw biomass was determined using the Chugaev reagent. Plant genotypes that are resistant to an excess of heavy metals in the medium and capable of active growth under stress were selected; A. tortuosum genotype № 6 exceeded the control by 2.6 times and reached a size of 46.7 mm (200 µM Zn2+). Plants showed an accumulating ability with respect to nickel ions in vitro. Genotype № 5 A. obovatum accumulates 1.59 mg/g Ni2+ wet weight, which is 8 times higher than the control (200 µM Ni2+). This study confirms the promise of using plants from the genus Alyssum for phytoremediation. The final qualifying work of the master is 61 pages, 21 figures, 5 tables, 81 literary sources, of which 50 are Russian-speaking and 31 are English-speaking.

This thesis reports the cell culture establishment and a somatic cell selection system optimized for the isolation of chlorsulfuron-resistant variants in asparagus (Asparagus officinalis L.). The development of this cell selection system benefited the isolation of chlorsulfuron-resistant variants from an elite asparagus genotype. A cell culture system, suitable for somatic cell selection, was established for asparagus genotype CRD 168. Friable callus was initiated from etiolated shoots in darkness and used to produce a high density of single cells in suspension. Cell density was estimated based on a linear relationship with settled cell volume. A mean plating efficiency of 0.19 % was recorded between 1-4x10⁵ cells/Petri dish. In vitro cell selection techniques were developed to identify mutant asparagus cells with resistance to a sulfonylurea herbicide, chlorsulfuron. A few key aspects were important to achieve this: a cell culture system for cell selection was initially established; a toxic concentration for the complete growth inhibition of the wild type asparagus cells was defined; rare, resistant cell colonies were isolated and characterized; and chlorsulfuron-resistant plants were regenerated. From about 50 million cells, 165 cell colonies were isolated in the presence of 8 nM chlorsulfuron. Characterization of these selected cell colonies yielded 24 escapes, 98 unstable variants, and 43 stable-resistant variants. Callus cultures from 34 of these stable variants retained resistance following 11 months growth in the absence of the selection agent. Plants were regenerated from 36 of these stable herbicide-resistant variants. Six of these chlorsulfuron-resistant variants were screened for their degree of resistance to chlorsulfuron, cross resistance to other acetohydroxyacid synthase (AHAS) inhibiting herbicides and AHAS enzyme activity. Cross resistance to imazamox was evident in four of the resistant variants, while lack of cross resistance to metsulfuron methyl was observed in all six resistant variants. A varying degree of resistance to chlorsulfuron was observed among the resistant variants. Both in the original and secondary callus, an uninhibited AHAS enzyme activity in all six resistant variants was recorded in the presence of high chlorsulfuron concentration (70-140 nM), compared to the total inhibition in the wild type. One chlorsulfuron-resistant variant, R-45, was used to compare the biochemical and physiological basis of resistance with the wild type. The AHAS enzyme activity in the tissue culture and greenhouse foliage of R-45 was significantly higher in the presence of up to 280 nM chlorsulfuron compared with the wild type. Chlorsulfuron retention was considerably higher due to the reduction of epicuticular wax deposits on the foliage of R-45, in comparison with the wild type. Consequently, the resistant line absorbed at least 1.6 fold more chlorsulfuron than the wild type plants. Therefore, foliar application of 15 g a.i./ha Glean (commercial formulation of chlorsulfuron) produced typical symptoms of chlorosis in R-45, similar to the wild type, in the greenhouse plants. Somatic cell selection was carried out using two elite asparagus genotypes, CRD 74 and Clone X. Of the 33 rare cell colonies isolated from Clone X, 22 unstable variants and 6 escapes were discarded. All five remaining resistant variants produced plants. One of the stable-resistant variants (Clone X-24) was evaluated for resistance to chlorsulfuron. Both in vitro shoot cultures and greenhouse-grown plants of Clone X-24 showed increased resistance to chlorsulfuron compared with the wild type. The AHAS enzyme activity in the foliar extracts also showed the presence of higher enzyme activity in Clone X-24.

The aim of this work is to define relations between grain size and bioaktivity of oxide ceramics, specifically ZrO2, Al2O3 and HA. Ceramic materials with grain size from 100 nm up to 10 m, with various surface roughness, were tested for its bioactivity. Ceramography analysis was performed for all tested materials to precisely describe microstructures. Biological properties of the ceramic materials were tested via dilation tests directly in-vitro and by in-vitro extraction. Three cell culturing lines: osteoblast MG63, fibroblast L929, and epithelioid HeLa, were used for our testing. An influence of the grain size on the biological response was only found for the ceramic materials which had been thermally etched. The thermally etched nanocrystalline samples had larger areas covered by cells than ceramics with coarse grain microstructure. Biological tests on layered composites Al2O3×ZrO2 showed the cell selection determined by the type of material, where ZrO2 surfaces were preferably covered. Improved biological response of nanocrystalline ZrO2 was demonstrated on ceramic ZrO2, Al2O3 and SiO2 substrates with nanocrystalline coating of ZrO2. In this work a novel technological process for the formation of defect-free coatings was developed. Sintered coatings were tested using in-vitro technique with cell line HeLa, L929 and MG63 for up to 72 hours. The results of the biological tests of nanocrystalline coatings were consistent with results from the bulk nanocrystalline thermally etched ZrO2 ceramics.