Fabrication of Micropatterns for the Spatial Control of Cell Propagation and DIfferentiation

Challenges in the development of successful cell therapies involve engineering and control of cues to regulate the balance between differentiation and self-renewal. However, the complexity of architecture and function make this an intriguing problem in the context of forming functional connections. Here we present the design and fabrication of microstructured scaffolds that present a biomimetic framework along which neural cell lines can organize into oriented constructs. Specifically, we show microfabricated non-linear architectures that promote cellular fate related to propagation of human neuroblastoma cells and directed differentiation towards neurons. By mimicking biological networks that allow for spreading of the cells instead of confining them in a groove or a well, a nonlinear configuration can promote a relaxed, self-supportive cell niche. The tailoring of non-homogeneous adhesion sites via the geometry and the compliance and roughness of the substrate allows a versatile microenvironment that promotes propagation and neuronal differentiation

Practical Provably Secure Multi-node Communication

We present a practical and provably-secure multimode communication scheme in the presence of a passive eavesdropper. The scheme is based on a random scheduling approach that hides the identity of the transmitter from the eavesdropper. This random scheduling leads to ambiguity at the eavesdropper with regard to the origin of the transmitted frame. We present the details of the technique and analyze it to quantify the secrecy-fairness-overhead trade-off. Implementation of the scheme over Crossbow Telosb motes, equipped with CC2420 radio chips, shows that the scheme can achieve significant secrecy gain with vanishing outage probability. In addition, it has significant overhead advantage over direct extensions to two-nodes schemes. The technique also has the advantage of allowing inactive nodes to leverage sleep mode to further save energy.Comment: Proceedings of the IEEE International Conference on Computing, Networking and Communications (ICNC 2014

The effect of corporate governance on firm performance: The case of Arab spring in the Middle East

This study investigates the impact of the separate elements of corporate governance on enterprise financial performance explained in three separate models (ROA, ROE, and Debt Ratio) for non-financial companies present within the S&P Pan Arab Composite Index. The data on corporate governance choices includes 225 firms for ten years from 2006 to 2015 gathered from ORBIS, Reuters Eikon, Datastream, as well as, annual and board reports. The firms included in this study are all listed respective to their country’s stock exchange, which are present in eleven Arab countries namely: Bahrain, Egypt, Jordan, Kuwait, Lebanon, Morocco, Oman, Qatar, Saudi Arabia, Tunisia and United Arab Emirates. The corporate governance variables are divided into board structure variables, ownership structure variables, and controlled variables. Furthermore, the topic attempts to understand the significance of the Arab Spring uprising on firm performance using the ROA and ROE measurements and debt ratio as a measurement of firm leverage. Furthermore, the data is used to compare the corporate governance variables five years before the Arab Spring uprising to the five years during/after the uprising. Regression results are demonstrated in the form of models. Model 1 shows the effect of corporate governance on firm performance measured by ROA. Results show that there is a significant positive relationship with board size, institutional ownership, audit type on firm performance measured by ROA, also there a significant negative relationship with duality, foreign ownership, firm size and the revolution variable on firm performance measured by ROA. Model 2 shows the effect of corporate governance on firm performance measured by ROE. Results show that there is a significant positive relationship with board size, institutional ownership, audit type on firm performance measured by ROE, also there a significant negative relationship with duality, firm size and the revolution variable on firm performance measured by ROE. Model 3 shows the effect of corporate governance on firm performance measured by Debt Ratio. Results show that there is a significant positive relationship with director ownership, foreign ownership, firm size, foreign exchange rate and the revolution variable on firm performance measured by Debt Ratio, also there a significant negative relationship with duality, institutional ownership and firm age on firm performance measured by ROE. After conducing Mann-Whitney U test, results shows that the variables ROA, ROE, ownership concentration, director ownership, institutional ownership, foreign ownership, firm size, firm age, foreign exchange rate, outward foreign direct investment, inward foreign direct investment and GDP are all statistically significant. The variables ROA, ROE, foreign exchange rate, outward foreign direct investment and inward foreign direct investment were a higher mean rank before the Arab Spring uprising compared to during/after the Arab Spring uprising. On the other hand, the variables ownership concentration, director ownership, institutional ownership, foreign ownership, firm size, firm age and GDP were a higher mean rank during/after the Arab Spring uprising compared to before the Arab Spring uprising

Conceptualizing Blockchain in The Music Industry

As blockchain technology continues to evoke interest and engagement across companies, organizations, industries, and governments, the desire to integrate the technology is evident. The discussion around blockchain often implies promises of decentralization, transparency, and disruption. The music industry specifically has been noted to potentially gain from the implementation of blockchain, making it a great context for exploration: the industry is constructed of multiple stakeholders with complicated and often dysfunctional connections. This research aims to understand how blockchain is utilized in the context of music industry. It distinctively tries to understand the technical structure of the applied blockchain, the implications to business logic and structures, and lastly the long-term intersection of blockchain and the music industry. This research was conducted as a qualitative multiple-case study. With an inductive and intensive approach, the objective was to explore the use of blockchain in a holistic nature from the perspective of each case. The empirical data was collected from secondary whitepapers published by each case company. Each whitepaper detailed the technical and the business structure as it pertains to blockchain. The data revealed how blockchain governs engagement and the positioning of each stake-holder in the ecosystem and in relation to each other in the presence, or lack thereof, of blockchain. It was concluded that blockchain can be utilized in varying ways and to varying degrees. The consequential effects can be observed in the governance, structure, and business logic of each case, which this research showcases in detail. While this research was able to provide differing possibilities for use, it could not provide evidence of blockchain being mature enough for mass adoption, supporting arguments presented in previous research and theory.Blockchain-teknologian noustessa yhä tunnetummaksi, monen yrityksen ja tahon tavoitteena on tutkia tämän teknologian hyödyntämistä. Musiikkiteollisuus on erityisesti mainittu sopivan kyseiseen integroimiseen: musiikkiteollisuudessa on monia sidosryhmiä, joiden välillä on monimutkaisia ja usein ongelmallisia suhteita. Tämän tutkimuksen tavoitteena on ymmärtää blockchain-teknologian käyttö musiikkiteollisuudessa. Ymmärrys ulottuu tekniseen hyödyntämiseen, liiketoiminnallisiin seuraamuksiin ja musiikkiteollisuuden ja teknologian pitkäaikaiseen risteytymään. Tutkimus suoritettiin laadullisena monitapaustutkimuksena, jonka tarkoituksena oli kerätä kokonaisvaltainen ymmärrys blockchain-teknologian käytöstä jokaisen tapauksen näkökulmasta. Empiirinen data kerättiin sekundääriaineistosta, josta tuli ilmi jokaisen tapauksen tekninen ja liiketoiminnallinen malli. Aineistoa lähestyttiin induktiivisesti ja analysoitiin intensiivisesti. Tulokset paljastivat kuinka blockchain-teknologia ohjasi kanssakäymistä ja miten eri sidosryhmät asennoituivat teknologiaan ja toisiinsa nähden. Teknologiaa hyödynnettiin eri tavoilla ja eri laajuudella. Teknologian seurauksena jokaisessa tapauksessa ilmestyi huomattavia eroja tapausten hallinnoinnissa, rakenteissa ja liiketoiminnan logiikassa. Tämä tutkimus erittelee tarkasti jokaisen tapauksen tekniset yksityiskohdat ja niistä seuraavat edellä mainitut erot. Johtopäätöksenä kuitenkin todetaan, että tutkimuksessa esiintyvät tapaukset ovat vielä kehittymisvaiheessa, eivätkä voi näin puoltaa teknologian olevan valmiina täysmittaiseen adoptioon. Tämä osaltaan tukee teoriassa esiin tuotuja väitteitä teknologian epäkypsyydestä

Optimization of a New Array Noise Tool; Analysis & Interpretation of Case Studies of Down- Hole Leak Detection

This thesis is concerned with the optimization and analysis of new array noise tools. Various lab and field case studies are analyzed to test the capabilities and determine the optimum operating conditions of the new tool for leak detection purposes. The purpose of this study is to optimize the logging procedure of real-time array noise tool, selecting adequate gain parameters and frequency band in the processing phase, and to analyze the data acquired through multiple labs and field tests. The study methodology involved the following steps: 1. Performing lab and field tests for the tool in a range of different scenarios. 2. Carrying out multiple real-life case studies and provide interpretation using commercial software. The gain setting was optimized to obtain the best results through logging and adding additional auxiliary logging accessories was proven to enhance the acquisition process. Moreover, implementing proper logging procedure that suits the tool capabilities aid the analysis process and the objective was met successfully. The tool was tested and proved consistent results, which can be commercialized and used as real-time noise tool. The new array noise tool overcomes the limitations of the memory noise tool in which it will save both time and money on the oil companies and will be able to provide in situ answers for leak detection purposes

Characterizing of Robo downstream signalling to promote direct neurogenesis

The size and degree of folding of the mammalian cortex are pivotal factors that affect species’ cognitive abilities and sensorimotor skills. The cerebral cortex is the main region in the mammalian brain that governs complex cognitive behaviors. The development of the cortex depends on the amplification of neural stem cells (NSCs), neural progenitors (NPs) and the generation and differentiation of postmitotic neurons. There are two main types of NPs in the mouse neocortex (NCx): apical radial glia (aRGCs) and intermediate progenitor cells (IPCs). Robo receptors play an important role in regulating the amplification of cortical progenitors. The absence of Robo receptor signalling plus the alteration of the Notch signalling pathway in the mouse NCx leads to an overproduction of poorly functional IPCs. Ancient amniotic cortices exhibit a predominance of direct neurogenesis during development, where aRGCs produce neurons directly. Intriguingly, Robo receptors as well as Notch signalling play a major role in attenuating the mode of neurogenesis. This hypothesis was validated in several brain structures with phyletic antiquity, confirming that Robo receptors are essential in the shift towards indirect neurogenesis during the evolution and expansion of the cerebral cortex. However, little is known about the precise signalling cascade or interactors employed by Robo to initiate direct neurogenesis. In this thesis, we demonstrated the transcriptomic differences between the developing mouse NCx and OB (where direct neurogenesis is predominant in the OB vs NCx) using single cell RNA sequencing (scRNA). We showed aRGCs populations that are differently enriched between these regions. We traced lineage trajectories of indirect and direct neurogenesis, as well as validating the expression of several differentially expressed genes between the two regions. We used Robo intracellular domain (ICD)—this region is considered a constitutively active form of Robo receptor—and demonstrated the protein interactors that bind it. Following that, we demonstrated Robo ICD localization to the nucleus. We discovered that Robo conserved cytoplasmic domains play an important role in Robo ICD nucleocytoplasmic localization and direct neurogenesis induction in the mouse NCx. Next, we showed that Robo ICD localizes to chromatin, and causes transcriptional changes that occur upon the experimental gain of function of Robo ICD in the NCx and in vitro. Additionally, we showed that loss of function of Nup107, a nuclear pore complex (NPC) protein and one of Robo ICD protein interactors, induces direct neurogenesis in mouse NCx and chick lateral pallium. Taken together, our findings suggest the transcriptional role Robo ICD exerts by binding DNA and, consequently, its conserved role in moderating direct neurogenesis. El tamaño y el grado de plegamiento de la corteza cerebral son factores fundamentales que afectan a las capacidades cognitivas y habilidades sensoriomotoras de los mamíferos. La corteza cerebral es la principal región del cerebro que gobierna conductas cognitivas complejas. El desarrollo de la corteza depende de la amplificación de células madre neurales (CMN), progenitores neurales (PN) y de la generación y diferenciación de neuronas postmitóticas. Hay dos tipos principales de PN en la neocorteza o neocórtex (NCx) del ratón: las células de glía radial apical (CGRa) y las células progenitoras intermedias (CPI). Los receptores Robo juegan un papel importante en la regulación de la amplificación de los progenitores corticales. La ausencia de señalización del receptor Robo sumada a la alteración de la vía de señalización de Notch en el NCx de ratón conduce a una sobreproducción de CPI poco funcionales. La corteza de especies amniotas anteriores en la evolución a los mamíferos (como los reptiles y las aves) exhiben un predominio de neurogénesis directa durante el desarrollo, por el cual las CGRa producen neuronas directamente. Curiosamente, los receptores Robo, así como la señalización de Notch, desempeñan un papel importante en la atenuación de esta modalidad de neurogénesis a lo largo de la evolución. Esta hipótesis ha sido validada en varias estructuras cerebrales con antigüedad filética, confirmando que los receptores Robo son esenciales en el cambio hacia la neurogénesis indirecta durante la evolución y la consecuente expansión de la corteza cerebral. Sin embargo, se sabe poco sobre la cascada de señalización de Robo, así como de los mensajeros secundarios empleados por este receptor para iniciar el proceso de neurogénesis directa. En esta tesis, demostramos las diferencias transcriptómicas que existen entre el NCx y el bulbo olfatorio (BO) de ratón en desarrollo (sabiendo que la neurogénesis directa es predominante en BO frente al NCx). Para ello usamos la técnica de secuenciación de ARN de células individuales (single-cell RNA sequencing (scRNAseq) en inglés). Mostramos que hay poblaciones de RGCa que están diferentemente enriquecidas entre estas regiones. Trazamos trayectorias de linaje de neurogénesis indirecta y directa y validamos la expresión de varios genes expresados diferencialmente entre las dos regiones. Utilizamos el dominio intracelular (DIC) de Robo (esta región se considera una forma constitutivamente activa del receptor) y demostramos los mensajeros secundarios que se unen. Después, demostramos la localización del DIC de Robo en el núcleo. Descubrimos que sus dominios citoplasmáticos, muy conservados a lo largo de la evolución, tienen un papel importante en la localización núcleo-citoplasmática del DIC y la inducción directa de neurogénesis en el NCx de ratón. A continuación, mostramos que una vez en el núcleo, el DIC se une a la cromatina y provoca cambios transcripcionales que tienen como resultado una la ganancia de función de Robo tanto en el NCx como in vitro. Además, demostramos que la pérdida de función de Nup107, una proteína que forma parte del complejo del poro nuclear (CPN) además de ser una proteína de interacción del DIC de Robo, induce neurogénesis directa en el NCx de ratón y en el palio lateral de pollo. En conjunto, nuestros resultados sugieren el papel de modulación transcripcional que ejerce el DIC de Robo al unirse al ADN y, en consecuencia, su rol conservado a lo largo de la evolución en la disminución de la neurogénesis directa

Novel and Bioactive Natural Products from the Marine-Derived Endophytic Fungi : Coniothyrium cereale, Phaeosphaeria spartinae and Auxarthron reticulatum

The main goal of this study was to discover novel natural products with pharmacological potential by employing various biotechnological methods. Marine fungi have been identified as a promising resource for such molecules. In particular, fungi living in the inner tissue of marine algae and sponges (endophytes) were found capable of producing a structurally and with regard to their bioactivity, most intriguing array of compounds. This study thus focussed on the three marine-derived fungi Coniothyrium cereale, Phaeosphaeria spartinae and Auxarthron reticulatum. They were cultivated in artificial media mimicking the marine environment and investigated for their bioactive secondary metabolites. The investigation dealt with the isolation, identification and biological evaluation of the fungal natural products with emphasis on compounds exhibiting cytotoxic and antimicrobial activities. Additionally, natural products that inhibit proteases such as Human Leukocyte Elastase (HLE), and compounds with affinity toward cannabinoid receptors were explored. The extracts of C. cereale, P. spartinae and A. reticulatum were subjected to purification employing high-tech chromatographic techniques. The isolated metabolites were characterized based on the extensive spectroscopic measurements. Stereochemical assignments were done through X-ray crystallographic and CD spectral analysis. The identified compounds were then evaluated for their biological activities. Over all 36 interesting compounds, partly with unprecedented chemical structures and outstanding bioactivity were isolated from three different fungal strains. The detailed analysis of the marine endophytic fungus C. cereale resulted in a series of compounds with a polyketide skeleton, i.e. the phenalenones. From the structural point of view, the most interesting compounds are the nitrogenous metabolites, i.e. conio-azasirosterol, cereo-azasirosterol, cereolactam and cereoaldomine. Conio-azasirosterol and cereo-azasirosterol are most unusual heterodimers composed of two different skeletons of natural products. In compounds cereolactam and cereoaldomine the nitrogen is either forming a rare γ-lactam ring or imine group, respectively. The Conitothyrium metabolite cereoazulene is a unique dioxa-azulene derivative, probably of polyketide origin and formed through oxidative cleavage of a regular polyketide precursor molecule. The detailed analysis of the marine endophytic fungus Ph. spartinae resulted in a novel steroidal compound and a series of polyketides. Spartogesterone is an unusual steroid due to the presence of a carboxylic group at C-4 and the structural similarity to the hormone progesterone. Indeed, the human hormone progesterone has only recently (2010) been discovered in plants, and the finding in our study suggests that progesterone derivatives also do occur in fungi. The polyketides spartinols A-D are characterized by the presence of a central cyclohexene ring to which two side chains are attached, long one with a trans triene system and another short one, substituted with hydroxyl-, carbonyl- and /or carboxyl group. This side chain also can be cyclized to form a furanoid ring, as seen in furanospartinol and a pyranoid ring as present in pyranospartinol. Pyranospartinol is also different from the aforementioned metabolites by having a cis diene double bond instead of a trans triene. Spartinoxide which was also obtained from this fungus has an uncommon allene moiety and epoxy group. From the fungus A. reticulatum two promising alkaloids were obtained, i.e. amauromine and methyl-penicinoline. Amauromine is an alkaloid with a C-2 axis of symmetry. It is composed of two prenylated tryptophan moieties, which are condensed to form a diketopiperazine nucleus. Methyl-penicinoline is a structurally unique 4-quinolinone, linked to a pyrrole ring on one side and to a methyl carboxylic acid ester moiety on the other. In antimicrobial assays, compounds conioscleroderolide, coniosclerodione, (–)-cereolactone, and (–)-scleroderolide showed activity against Staphylococcus aureus SG 511 with MIC values of 23.8, 65.7, 52.0, and 23.8 μM, respectively. In agar diffusion assays with Mycobacterium phlei considerable inhibition zones (> 15 mm) were observed for Z-coniosclerodinol, (S,S)-sclerodinol and coniolactone. (–)-Trypethelon strongly inhibited the growth of M. Phlei, S. Aureus and E. coli with inhibition zones of 18, 14 and 12 mm, respectively. In cytotoxic assays, using an MTT assay with mouse fibroblast cells, the compounds (–)-sclerodione and (–)-trypethelone had significant activity with an IC50 value of 6.4 and 7.5 µM, respectively. Cytotoxicity was also determined using an epithelial bladder carcinoma cell line, in which the compounds conioscleroderolide and (–)-scleroderolide exhibited very weak in vitro cytotoxicity with IC50 values of 27 and 41 μM, respectively. Coniosclerodin, conioscleroderolide, (–)-sclerodin, (–)-cereolactam, (–)-cereoaldomine, spartinoxide and prenyl-hydroxyl-benzoic acid showed potent inhibition of the protease HLE with IC50 values of 7.16, 13.3, 10.9, 9.28, 3.01, 6.5 and 8.1 μM, respectively. Amauromine displayed a potent and selective antagonistic activity toward CB1 receptors with a Ki value of 178 nM. No affinity was noted for CB2 receptors. To the best of our knowledge, amauromine is the first compound of fungal origin to have affinity to cannabinoid receptors, and it is the first exogenous peptide to have such an activity. In conclusion, the chemical investigation of marine fungi living in algal and sponge tissues resulted in the discovery of structurally novel natural products with interesting biological activities. In fact this study contributed novel structural skeletons probably useful as lead drugs for the development of cytotoxic antibiotic compounds, protease inhibitors and cannabinoid receptor antagonists

New Synthetic Methodologies Directed toward Pharmacologically Active Compounds as well as Silole Based Chromophores for Analytical and Optoelectronic Applications

The development of new and efficient synthetic methodologies to prepare heterocyclic compounds has received great attention over the years due to their importance in the pharmaceuticals and fine chemicals industries. Described herein are several novel syntheses of a variety of heterocycles including siloles, azaindoles, piperideines, piperidines and tetrahydropyrans. A one-pot, two-step methodology involving Tamao’s reductive cyclization followed by Negishi cross coupling was utilized to synthesize several new series of silole-based chromophores. The property studies revealed new electropolymerized poly(thienyl-silole)s with enhanced photoefficiency for all-polymer solar cells. In addition, a new procedure is developed for the synthesis of the first dissymmetric silole tethered to amine functionality. The synthesized compounds hold great promise in the arena of biosensors and solar cell applications. Furthermore, a novel and practical two step sequence for the preparation of C2 substituted 5-azaindoles has been reported. The synthetic sequence features a [3+2] dipolar cycloaddition between nitriles and a 3,4-cyclopropanopiperidine followed by SeO2 oxidation. Finally, the annulation reaction between 2-alkoxy-1,1-cyclobutane diesters and imines or aldehydes gave access to highly functionalized piperidines and tetrahydropyrans, respectively. Both the synthesis of those donor-acceptor cyclobutanes and their subsequent annulations are catalyzed by catalytic Yb(OTf)3. Although known for more than two decades, this is the first use of 2-alkoxy-1,1-cyclobutane diesters in dipolar cycloadditions. The new reactions are done under mild conditions providing the target compounds in high yields and excellent selectivity. The divergent nature and cost effectiveness of these methods make them very suitable for combinatorial applications in the pharmaceutical industry