Development of Molecular Contrast-enhanced Imaging for Optical Coherence Tomography

Biological imaging techniques that are able to detect a contrast-enhanced signal from the target molecules have been widely applied to various techniques in the imaging field. The complex biological environment provides numerous and more efficient pathways along which the chromophores (light absorber) may release its energy. This energy can provide not only morphological information, but also specific molecular information such as a biochemical map of a sample. All diseases correlate with both morphological and biochemical changes. Optical coherence tomography (OCT) system is one of the biological imaging techniques. OCT has widely been applied to many medical/clinical fields, giving benefit from a penetration depth of a few millimeters while maintaining a spatial resolution on the order of a micron. Unfortunately, OCT lacks the straightforward functional molecular imaging extensions available for other technologies, e.g. confocal fluorescence microscopy and fluorescence diffuse optical tomography. This is largely because incoherent processes such as fluorescence emission and Raman scattering are not readily detectable with low coherence interferometry that is the central technique that underlies all OCT systems. Despite a drawback of molecular imaging with OCT, it is highly desirable to measure not only morphological, but also molecular information from either endogenous or exogenous molecules. In order to overcome the limitation of molecular contrast imaging for OCT, our group has been researched the hybrid OCT imaging technique and a new exogenous contrast agent. Our contrast-enhanced imaging technique integrates OCT with a well-researched and well-established technique: two-colored pump-probe absorption spectroscopy. Our novel imaging technique is called Pump-Probe OCT (PPOCT). Based upon current successful results, molecular imaging with OCT potentially gives us the ability to identify pathologies. In order to expand the capacity of PPOCT, this dissertation focuses on development of molecular contrast-enhanced imaging for optical coherence tomography (OCT). In the first phase of the research, we developed and optimized for sensitivity a two-color ground state recovery Pump-Probe Optical Coherence Tomography (gsrPPOCT) system and signal algorithm to measure the contrast-enhanced signal of endogenous and exogenous contrast agents such as Hemoglobin (Hb) and Methylene blue (MB) from in vivo samples. Depending on the absorption peak of a target molecule, the pump light sources for PPOCT used 532nm Q-switched laser or 663nm diode laser. Based on different experimental application, Ti:sapp or SLD of 830nm center wavelength were utilized. The PPCOT system was firstly used to image Hb of in vivo vasulature in a Xenopus laevis as the endogenous contrast agent and a larval stage zebrafish using MB as the exogenous contrast agent via transient changes in light absorption. Their morphological in addition to molecular specific information from a live animal was described. The incorporation of a pump laser in an otherwise typical spectrometer based OCT system is sufficient to enable molecular imaging with PPOCT. In the second phase of this research, based on endoscopic molecular contrast-enhanced applications for OCT, we invented an ultra-wideband lensless fiber optic rotary joint based on co-aligning two optical fibers has excellent performance (~0.38 dB insertion loss). The developed rotary joint can cover a wavelength range of at least 355- 1360 nm with single mode, multimode, and double clad fibers with rotational velocities up to 8800 rpm (146 Hz). In the third phase of this research, we developed and manufactured a microencapsulated methylene blue (MB) contrast agent for PPOCT. The poly lactic coglycolic acid (PLGA) microspheres loaded with MB offer several advantages over bare MB. The microsphere encapsulation improves the PPOCT signal both by enhancing the scattering and preventing the reduction of MB to leucomethylene blue. The surface of the microsphere can readily be functionalized to enable active targeting of the contrast agent without modifying the excited state dynamics of MB that enable PPOCT imaging. Both MB and PLGA are used clinically. PLGA is FDA approved and used in drug delivery and tissue engineering applications. 2.5 µm diameter microspheres were synthesized with an inner core containing 0.01% (w/v) aqueous MB. As an initial demonstration the MB microspheres were imaged in a 100 µm diameter capillary tube submerged in a 1% intralipid emulsion. By varying the oxygen concentration both 0% and 21%, we observed he lifetime of excited triple state using time-resolved Pump-Probe spectroscopy and also the relative phase shift between the pump and probe is a reliable indicator of the oxygen concentration. Furthermore, these results are in good agreement with our theoretical predictions. This development opens up the possibility of using MB for 3-D oxygen sensing with PPOCT

Development of Molecular Contrast-enhanced Imaging for Optical Coherence Tomography

Biological imaging techniques that are able to detect a contrast-enhanced signal from the target molecules have been widely applied to various techniques in the imaging field. The complex biological environment provides numerous and more efficient pathways along which the chromophores (light absorber) may release its energy. This energy can provide not only morphological information, but also specific molecular information such as a biochemical map of a sample. All diseases correlate with both morphological and biochemical changes. Optical coherence tomography (OCT) system is one of the biological imaging techniques. OCT has widely been applied to many medical/clinical fields, giving benefit from a penetration depth of a few millimeters while maintaining a spatial resolution on the order of a micron. Unfortunately, OCT lacks the straightforward functional molecular imaging extensions available for other technologies, e.g. confocal fluorescence microscopy and fluorescence diffuse optical tomography. This is largely because incoherent processes such as fluorescence emission and Raman scattering are not readily detectable with low coherence interferometry that is the central technique that underlies all OCT systems. Despite a drawback of molecular imaging with OCT, it is highly desirable to measure not only morphological, but also molecular information from either endogenous or exogenous molecules. In order to overcome the limitation of molecular contrast imaging for OCT, our group has been researched the hybrid OCT imaging technique and a new exogenous contrast agent. Our contrast-enhanced imaging technique integrates OCT with a well-researched and well-established technique: two-colored pump-probe absorption spectroscopy. Our novel imaging technique is called Pump-Probe OCT (PPOCT). Based upon current successful results, molecular imaging with OCT potentially gives us the ability to identify pathologies. In order to expand the capacity of PPOCT, this dissertation focuses on development of molecular contrast-enhanced imaging for optical coherence tomography (OCT). In the first phase of the research, we developed and optimized for sensitivity a two-color ground state recovery Pump-Probe Optical Coherence Tomography (gsrPPOCT) system and signal algorithm to measure the contrast-enhanced signal of endogenous and exogenous contrast agents such as Hemoglobin (Hb) and Methylene blue (MB) from in vivo samples. Depending on the absorption peak of a target molecule, the pump light sources for PPOCT used 532nm Q-switched laser or 663nm diode laser. Based on different experimental application, Ti:sapp or SLD of 830nm center wavelength were utilized. The PPCOT system was firstly used to image Hb of in vivo vasulature in a Xenopus laevis as the endogenous contrast agent and a larval stage zebrafish using MB as the exogenous contrast agent via transient changes in light absorption. Their morphological in addition to molecular specific information from a live animal was described. The incorporation of a pump laser in an otherwise typical spectrometer based OCT system is sufficient to enable molecular imaging with PPOCT. In the second phase of this research, based on endoscopic molecular contrast-enhanced applications for OCT, we invented an ultra-wideband lensless fiber optic rotary joint based on co-aligning two optical fibers has excellent performance (~0.38 dB insertion loss). The developed rotary joint can cover a wavelength range of at least 355- 1360 nm with single mode, multimode, and double clad fibers with rotational velocities up to 8800 rpm (146 Hz). In the third phase of this research, we developed and manufactured a microencapsulated methylene blue (MB) contrast agent for PPOCT. The poly lactic coglycolic acid (PLGA) microspheres loaded with MB offer several advantages over bare MB. The microsphere encapsulation improves the PPOCT signal both by enhancing the scattering and preventing the reduction of MB to leucomethylene blue. The surface of the microsphere can readily be functionalized to enable active targeting of the contrast agent without modifying the excited state dynamics of MB that enable PPOCT imaging. Both MB and PLGA are used clinically. PLGA is FDA approved and used in drug delivery and tissue engineering applications. 2.5 µm diameter microspheres were synthesized with an inner core containing 0.01% (w/v) aqueous MB. As an initial demonstration the MB microspheres were imaged in a 100 µm diameter capillary tube submerged in a 1% intralipid emulsion. By varying the oxygen concentration both 0% and 21%, we observed he lifetime of excited triple state using time-resolved Pump-Probe spectroscopy and also the relative phase shift between the pump and probe is a reliable indicator of the oxygen concentration. Furthermore, these results are in good agreement with our theoretical predictions. This development opens up the possibility of using MB for 3-D oxygen sensing with PPOCT

Simulated horizontal mergers in vertically related markets

Thesis (MCom)--Stellenbosch University, 2022.ENGLISH SUMMARY: A global trend of increasing retail concentration and a heightened concern about buyer power demand more sophisticated and flexible merger screening tools. Parametrisable merger simulation models that suitably account for the effects of bargaining competition may pose a solution. Thus, this dissertation examines the predicted effects o f retail consolidation in a vertically related market using the merger simulation tool developed by Tschantz and Froeb (2019). With the flat logit nested demand function for differentiated products of Boshoff e t a l. (2020), the predicted retail merger effects of five different bargaining and non-bargaining models for a 1 × 2 industry are evaluated. The primary contribution of this study is its unique application of Nashin-Shapley (NiS) bargains in the study of retail consolidation. It is novel in so far it compares the inherent implications of Nash-in-Nash (NiN) and NiS bargains for the appraisal of retail mergers. Pre-merger competitive outcomes with NiN predetermine a finding o f an anticompetitive merger. Contrarily, predictions with NiS as its starting point do not indicate that a merger would cause consumer harm, and therefore, would not be prohibited. In addition, the results suggest that retail consolidation consistently poses a viable option through which retailers can improve their profitability and bargaining positions. However, merger incentives are moderated by the competitiveness of an outside market.AFRIKAANSE OPSOMMING: ’n Globale tendens van toenemende konsentrasie in die kleinhandelsektor en ’n verhoogde kommer oor koopkrag verg noodsaaklikerwys meer gesofistikeerde en aanpasbare samesmelting siftingsmetodes. Parameteriseerbare modelle van gesimuleerde samesmeltings wat op ’n geskikte wyse van die effekte van b edinging e n mededinging rekening hou, mag ’n oplossing bied. Dus, bestudeer hierdie proefskrif die effek van konsolidasie in ’n vertikaal verwante kleinhandelsektor met die gebruik van die samesmelting-simulasiemetode van Tschantz en Froeb (2019). Met die gebruik van die “flat logit nested” vraagfunksie vir gedifferensieerde produkte van Boshoff et al. (2020) word die uitkomste van vyf verskillende bedinging en nie-bedinging modelle vir ’n 1 × 2 industrie evalueer. Die primêre bydra van hierdie studie is sy unieke toepassing van Nash-in-Shapley (NiS) bedinging in die bestudering van konsolidasie in die kleinhandelsektor. Die studie is oorspronklik aangesien hierdie aanwending ’n kritiese vergelyking van die inherente implikasies van Nash-in-Nash (NiN) en NiS bedinging vir die beoordeling van samesmeltings toelaat. Pre-samesmelting NiN-modelle genereer toestande van oordrewe mededinging en sal daarom ’n bevinding van ’n anti-mededingende samesmelting vooraf bepaal. In teenstelling, sal ’n kleinhandel-samesmelting met NiS as sy beginpunt nie skade aan die verbruiker daarstel nie en sal daarom nie verbied word nie. Boonop, suggereer hierdie resultate dat kleinhandel-samesmeltings deurgaans ’n lewensvatbare opsie waardeur kleinhandelaars hul winsgewendheid en bedingingsposisie kan verbeter, bied. Daarbenewens, word die aansporings om saamte smelt deur die mededingendheid van ’n buite-mark gemodereer.Master

Utilization of Partially Purified Papain Enzyme in Mallika Black Soybean Tempeh Hydrolysate as Umami Seasoning

Tempeh made from Mallika black soybean (Glycine max (L.) Merr. var. Mallika) can be fermented for up to 4 days and can be further optimized by adding partially purified papain enzyme obtained from California variety papaya leaves (Carica papaya (L.) var. California). Enzyme can be added to the hydrolysates to degrade protein into short-chain peptides and free amino acids, contributing to umami taste sensory attributes. The study aimed to determine the best ammonium sulfate fractionation of crude papain enzyme and the best physicochemical characteristics of black soybean tempeh protein hydrolysate. The addition of ammonium sulfate fractionation used was 0% to 80%; fermentation time was 2 to 4 days; and the concentration of enzyme added was 0%(w/v) to 1.5%(w/v). The results showed that the 40% fractioned papain enzyme gave the highest protease activity value (0.98±0.04 U ml-1) and most of the papain enzyme was precipitated in this fraction leaving impurities. The black soybean tempeh hydrolysates with 4 × 1% showed the best physicochemical characteristic because it produced the highest umami substance. The best characteristics were moisture content (17.97±0.46%), glutamic acid content (171.58±5.72 mg g-1) that was caused by a transamination reaction, dissolved protein content (470.66±19.50 mg g-1), degree of hydrolysis (43.64±1.99%) and lightness (46.02±0.97). The umami substance’s amino acids are high in content, such as glutamic and aspartic acids (59.89±0.31 mg g-1 and 26.47±0.09 mg g-1). Sensory evaluation showed that treatment 4 × 1% demonstrated no significant difference in umami intensity with MSG (monosodium glutamate)

Generierung und Charakterisierung humaner Oligodendroglia als zelluläres Modell für die Multisystematrophie

Multiple system atrophy (MSA) is a rare and devastating movement disorder with a fast progressive and fatal disease course. Patients present a heterogeneous combination of clinical symptoms including parkinsonism, cerebellar ataxia and autonomic failure. The accumulation of alpha - synuclein (aSyn) within oligodendroglial cytoplasmic inclusions (GCIs) is an important neuropathological hallmark of the disease and has been associated with demyelination and widespread neurodegeneration. Myelin is formed by specialized membranes of oligodendrocytes and represents an abundant and crucial structure of the central nervous system. Continuous physiological myelin turnover, adaptive myelination and remyelination are critical for neuronal survival and brain plasticity. Disturbances in the myelin homeostasis result in signal transmission delay, breakdown of metabolic support and ultimately the degeneration of axons and neurons. Although the precise cascade of pathogenic events remains elusive, oligodendrocytes are considered as the primary affected cell type in MSA. Rodent in vitro studies indicated aSyn as an inhibitor of oligodendroglial maturation and myelination, however, little is known about its impact on human oligodendroglia. A severe myelin deficit is present in MSA brain tissue without a concurrent loss of oligodendrocytes leading to the hypothesis that intracellular accumulation of aSyn interferes with the myelinating capacity of oligodendrocytes. A human cellular model for MSA was established to address this hypothesis. Human induced pluripotent stem cells were derived from healthy donors and oligodendroglial lineage specification induced by the ectopic expression of the oligodendroglial transcription factors OLIG2, SOX10, and NKX6.2. Oligodendroglial identity and terminal maturation was confirmed by a thorough phenotypical characterization based on transcriptional, morphological and metabolome analyses. Notably, a profound upregulation of the lipid metabolism during in vitro differentiation of human oligodendrocytes was identified by applying liquid chromatography - tandem mass spectrometry. Ultimately, oligodendrocytes ensheathed inert nanofibers in vitro supporting a myelinating potential of these cells. The origin of aSyn in GCIs is controversially debated. Human oligodendrocytes expressed aSyn and incorporated recombinant aSyn from the supernatant, which corroborates both, an endogenous and exogenous origin of aSyn. Lentiviral particles were used to increase intracellular levels of aSyn. Accumulating aSyn was distributed across the cell with an enrichment in the perinuclear cytoplasm, yet without forming GCI - like inclusions. The differentiation into oligodendroglial lineage cells was not affected by aSyn and myelin gene expression was largely preserved except for a decline in transcripts of the mature myelin basic protein. Nevertheless, aSyn accumulation led to a myelin deficit in vitro. Oligodendrocytes extended less primary processes to ensheath nanofibers while the length of individual myelin - like segments was unaltered or even increased. A significant number of aSyn expressing oligodendrocytes presented an immature morphology despite immunoreactivity for the mature myelin basic protein. Morphological changes were accompanied by an increase in actin filaments and cell body enlargement. Actin remodeling is a critical event during oligodendroglial differentiation and myelination. Membrane protrusion and process outgrowth require the local assembly of actin bundles, however widespread polymerization acts as physical barrier and increases membrane tension. No effects of aSyn on cell body stiffness were identified, but a profound reduction in Ermin expression. Considering the role of Ermin in cytoskeletal remodeling and myelin maintenance, the transcriptional repression of Ermin provides a potential link between altered actin dynamics, reduced process outgrowth and myelin deficits. Finally, actin dynamics during oligodendroglial differentiation were assessed using phalloidin staining. Premature oligodendrocytes were enriched in actin filaments, which became partially disassembled or redistributed to the cellular rim during maturation. Latrunculin A - mediated depolymerization of actin structures facilitated process outgrowth and arborization. These findings suggest that membrane protrusion not only depends on actin polymerization but also requires local disassembly. In conclusion, a human cellular model for MSA was established to decipher potential pathomechanisms downstream of aSyn accumulation. The results obtained in this thesis suggest a pathogenic link between aSyn accumulation, actin remodeling and myelin disturbances, thus pointing toward a novel pathogenic cascade with potential implication in MSA - related pathogenesis. By resembling aSyn - induced myelin deficits, the current disease model represents a very valuable tool for preclinical MSA research and will help to evaluate promising candidates for interventional therapies. Ultimately, the established protocol for the generation of human oligodendroglia allows a broad application in basic research and high - throughput drug screenings.Die Multisystematrophie (MSA) ist eine seltene Bewegungsstörung mit einem schnell - fortschreitenden und letalem Verlauf. Die klinischen Symptome können sehr heterogen sein und umfassen neben Parkinson - ähnlichen Symptomen auch zerebellare ataktische Störungen sowie eine schwere autonome Dysfunktion. Die Anreicherung von alpha - Synuclein (aSyn) in oligodendroglialen zytoplasmatischen Einschlüssen (GCIs) stellt ein wichtiges neuro-pathologisches Merkmal dar, welches darüber hinaus mit einem ausgeprägten Myelinverlust und einer weitreichenden Neurodegeneration in Verbindung gebracht wurde. Myelin ist ein essenzieller Bestandteil des Zentralnervensystems. Es wird durch spezialisierte Membranen von Oligodendrozyten gebildet. Ein kontinuierlicher Myelinumsatz, sowie adaptive Myelinisierung und Remyelinisierung sichert das Überleben von Neuronen und trägt zu einer lebenslangen Anpassungsfähigkeit des Gehirns bei. Störungen in der Myelinhomöostase führen zu einer verzögerten Signalübertragung, einer verringerten metabolischen Unterstützung und ultimativ zu degenerativen Veränderungen von Axonen und Neuronen. Obwohl der genaue Ablauf pathogener Ereignisse nicht bekannt ist, werden in der MSA Oligodendrozyten als der primär betroffene Zelltypus angesehen. Murine Zellkulturstudien deuten darauf hin, dass aSyn die Ausreifung von Oligodendrozyten sowie das Ausbilden von Myelinscheiden beeinträchtigt. Über die Auswirkungen auf humane Oligodendroglia ist jedoch wenig bekannt. Neuropathologisch zeigt sich ein schweres Myelindefizit in MSA Gehirnen, jedoch ohne einen proportional dazu vergleichbaren Verlust an Oligodendrozyten. Dies führte zu der Hypothese, dass die Myelinsierungskapazität von Oligodendrozyten durch die intrazelluläre Anreicherung von aSyn beeinträchtig wird. Es wurde ein humanes Zellkulturmodell für die MSA generiert, um diese Hypothese zu untersuchen. Dafür wurden humane induzierte pluripotente Stammzellen von gesunden Spendern generiert und die oligodendrogliale Differenzierung durch eine ektopische Expression der oligodendroglialen Transkriptionsfaktoren OLIG2, SOX10 und NKX6.2 induziert. Die Differenzierung sowie das Ausreifen von Oligodendrozyten wurde durch eine detaillierte phänotypische Charakterisierung bestätigt. Neben Expressionsanalysen wurde auch morphologische und metabolomische Untersuchungen durchgeführt. Während der Differenzierung humaner Oligodendrozyten wurde mittels Flüssigkeitschromatographie und Tandem - Massenspektrometrie eine starke Zunahme des Lipidstoffwechsels festgestellt. Darüber hinaus konnte gezeigt werden, dass Oligodendrozyten inerte Nanofasern umhüllen und daher ein Myeliniserungspotential besitzen. Der Ursprung von aSyn in GCIs wird kontrovers diskutiert. Humane Oligodendrozyten exprimierten aSyn und nahmen rekombinantes aSyn aus dem Überstand auf, wodurch die Annahme eines endogenen als auch eines exogenen Ursprungs nachvollziehbar erscheint. Lentivirale Partikel wurden genutzt, um die intrazelluläre aSyn Konzentration zu erhöhen. Das exprimierte aSyn verteilte sich über die gesamte Zelle, reicherte sich jedoch im perinukleären Zytoplasma an. Es wurden keine GCI - ähnlichen Einschlüsse gebildet. Die Differenzierung zu Oligodendrozyten wurde durch aSyn nicht beeinträchtig und die Expression von Myelin - assoziierten Genen blieb überwiegend konstant. Eine Ausnahme stellte dabei das basische Myelinprotein (MBP) dar, bei dem sich weniger Transkripte zeigten. Zusätzlich konnte ein Myelindefizit festgestellt werden. Oligodendrozyten bildeten weniger Fortsätze aus, um Nanofasern zu umhüllen. Die Länge einzelner Myelin - ähnlicher Segmente blieb dabei jedoch unverändert oder nahm sogar zu. Eine Vielzahl von aSyn exprimierenden Oligodendrozyten zeigte eine unreife Morphologie, trotz positiver Färbung für das reife Myelinprotein MBP. Neben den morphologischen Veränderungen, konnte auch eine Zunahme an Aktinfilamenten und eine Zellvergrößerung beobachtet werden. Die Restrukturierung des Aktin - Zytoskeletts ist eine wichtige Voraussetzung für die Differenzierung von Oligodendrozyten und die Bildung von Myelinscheiden. Die lokale Ausbildung von Aktinbündeln begünstigt die Bildung von Membranausstülpungen und fördert das Wachstum von Fortsätzen. Eine diffuse und weitreichende Polymerisierung von Aktin stellt dagegen eine physikalische Barriere dar und trägt zu einer erhöhten Zellmembranspannung bei. Eine Anreicherung von aSyn führte nicht zu einer Versteifung der Zellen, jedoch konnte eine verminderte Expression von Ermin ermittelt werden. Das Protein Ermin ist an der Umstrukturierung von Aktin sowie der Aufrechterhaltung von Myelinscheiden beteiligt. Die verminderte Expression stellt daher eine mögliche Verbindung zwischen einer veränderten Aktin - Dynamik, einer reduzierten Fortsatzbildung und Myelindefiziten dar. Abschließend wurde die Aktin - Dynamik während der oligodendroglialen Differenzierung genauer betrachtet. Hierfür wurden Aktinfilamente mittels Phalloidinfärbung sichtbar gemacht. Unreife Oligodendrozyten wiesen eine erhöhte Menge an Aktinfilamenten auf. Im Verlauf der Ausreifung, wurden diese Strukturen jedoch zunehmend abgebaut oder an den Zellrand verlagert. Eine Depolymerisierung des Aktin - Zytoskeletts mittels Latrunculin A führte zu einem vermehrten Auswachsen von Zellfortsätzen und förderte die Fortsatzverzweigung. Diese Ergebnisse deuten darauf hin, dass die Fortsatzbildung nicht allein von einer gesteigerten Aktin - Polymerisierung abhängt, sondern auch ein lokaler Abbau erforderlich ist. Zusammenfassend konnte im Rahmen dieser Dissertation ein humanes Zellkulturmodell für die MSA etabliert werden mit dem Ziel mögliche aSyn - assoziierte Pathomechanismen zu entschlüsseln. Die in dieser Arbeit erhaltenen Ergebnisse deuten auf einen pathologischen Zusammenhang zwischen aSyn - Akkumulation, Aktin - Restrukturierung und Myelindefiziten hin, welches einen weiteren bisher unbekannten Pathomechismus in der MSA darstellt. Mittels des etablierten Krankheitsmodels konnte ein wesentliches Merkmal der MSA nachgestellt werden, ein aSyn assoziiertes Myelindefizit. Dadurch wird es zu einem wertvollen präklinischen Modell für die MSA - Forschung und kann genutzt werden, um vielversprechende Kandidaten für zukünftige therapeutische Interventionen zu testen. Darüber hinaus kann das etablierte Differenzierungsprotokoll eine breite Anwendung in der Grundlagenforschung sowie in High - Throughput Screenings für Wirkstoffe finden

Shelleyan monsters: the figure of Percy Shelley in Mary Shelley’s Frankenstein and Peter Ackroyd’s The Casebook of Victor Frankenstein

Magister Artium - MAThis thesis will examine the representation of the figure of Percy Shelley in the text of Mary Shelley’s Frankenstein (1818). My hypothesis is that Percy Shelley represents to Mary Shelley a figure who embodies the contrasting and more startling aspects of both the Romantic Movement and the Enlightenment era. This I will demonstrate through a close examination of the text of Frankenstein and through an exploration of the figure of Percy Shelley as he is represented in the novel. The representation of Shelley is most marked in the figures of Victor and the Creature, but is not exclusively confined to them. The thesis will attempt to show that Victor and the Creature can be read as figures for the Enlightenment and the Romantic movements respectively. As several critics have noted, these fictional protagonists also represent the divergent elements of Percy Shelley’s own divided personality, as he was both a dedicated man of science and a radical Romantic poet. He is a figure who exemplifies the contrasting notions of the archetypal Enlightenment man, while simultaneously embodying the Romantic resistance to some aspects of that zeitgeist. Lately, there has been a resurgence of interest in the novel by contemporary authors, biographers and playwrights, who have responded to it in a range of literary forms. I will pay particular attention to Peter Ackroyd’s, The Casebook of Victor Frankenstein (2011), which shows that the questions Frankenstein poses to the reader are still with us today. I suggest that this is one of the main impulses behind this recent resurgence of interest in Mary Shelley’s novel. In particular, my thesis will explore the idea that the question of knowledge itself, and the scientific and moral limits which may apply to it, has a renewed urgency in early 21st century literature. In Frankenstein this is a central theme and is related to the figure of the “modern Prometheus”, which was the subtitle of Frankenstein, and which points to the ambitious figure who wishes to advance his own knowledge at all costs. I will consider this point by exploring the ways in which the tensions embodied by Percy Shelley and raised by the original novel are addressed in these contemporary texts. The renewed interest in these questions suggests that they remain pressing in our time, and continue to haunt us in our current society, not unlike the Creature in the novel

Pengembangan Modul Dasar-dasar Mesin

This study aimed to describe the module before developing, to produce the basics engine module, to analyze the effectiveness of module, to analyze the efficiency of module, and to analyze the attractiveness of modules. Test subject matter  compose of a single expert, one expert instructional design, three students for individual trials, six students for small group testing, and twenty-six students for field testing at SMK Muhammadiyah 2 Metro, twenty-eight students at SMK KP Gajah Mada 2 Metro. The result of this research are teaching materials produced in the learning modules form validated by experts and expert content and instructional design, the effectiveness of the learning module is shown by a mean score of 7.69Penelitian ini bertujuan untuk mendeskripsikan modul sebelum pengembangan, menghasilkan modul dasar-dasar mesin, menganalisis efektivitas modul, menganalisis efisiensi modul, dan menganalisis daya tarik modul. Subjek ujicoba terdiri dari satu ahli materi, satu ahli desain pembelajaran, tiga siswa untuk uji perorangan, enam siswa untuk uji kelompok kecil, dan dua puluh enam siswa untuk uji lapangan pada SMK Muhammadiyah 2 Metro, dua puluh delapan siswa pada SMK KP Gajah Mada 2 Metro. Hasil penelitian ini adalah bahan ajar yang dihasilkan berupa modul pembelajaran divalidasi oleh ahli materi dan ahli desain pembelajaran, efektivitas modul pembelajaran ditunjukkan dengan rerata skor 7.69

Trapping light in air with membrane metasurfaces for vibrational strong coupling

Optical metasurfaces can manipulate electromagnetic waves in unprecedented ways at ultra-thin engineered interfaces. Specifically, in the mid-infrared (mid-IR) region, metasurfaces have enabled numerous biochemical sensing, spectroscopy, and vibrational strong coupling (VSC) applications via enhanced light-matter interactions in resonant cavities. However, mid-IR metasurfaces are usually fabricated on solid substrates, which degrade resonance quality factors (Q) and hinder efficient sample access to the near-field electromagnetic hotspots. Besides, typical IR-transparent substrate materials, such as CaF2, NaCl, KBr, and ZnSe, are usually either water-soluble, expensive, or not compatible with low-cost mass manufacturing processes. To address these substrate-related technological limitations, we present novel substrate-less mid-IR metasurfaces with strong light-trapping capabilities in accessible air voids through the patterning of free-standing Si-membranes. We employed the Brillouin zone folding technique to excite high-Q quasi-bound states in the continuum (q-BIC) resonances. Leveraging the strong field localizations in accessible air cavities (|E/E0|>200), we demonstrated VSC between molecules and the q-BIC modes. Our new approach of fabricating mid-IR metasurfaces into semiconductor membranes enables low-cost manufacturing of MIR photonic devices and provides exciting opportunities for quantum-coherent light-matter interactions, biochemical sensing, and polaritonic chemistry

The increased use of information and communication technology (ICT) among employees: Implications for work-life interaction

Technology has become one of society’s everyday functional tools, changing rapidly and providing widespread mobility. In South Africa alone, the number of Internet users grew from 8,5 million to 24,9 million in only three years (2011-2014). Currently, 90 per cent of these users access this facility from their mobile devices. Statistics illustrate that South Africans are moving towards a continuously connected lifestyle, a situation in which information and communication technology (ICT) seems to have become ubiquitous. Given the rapid growth of ITC technology and its absorption into people’s lives (both personally and professionally), the general aim of the present research was to investigate the use of ICT among employees and how it affects their work-life interaction (WLI). The researcher employed a qualitative research approach in accordance with which a sample of 25 employees was interviewed. Interviews were recorded, transcribed and processed by means of thematic analyses. Three themes with corresponding sub-themes were extracted: use of ICT (i.e. in both work and family domains); challenges that ICT use presents; and the way in which employees manage their WLI by means of ICT. The participants experienced WLI as mostly negative. However, they also mentioned two different approaches that helped them manage interaction between their work and family domains. These approaches entail 1) applying limits to their use of ICT, and 2) using ICT to create flexibility. This article advises that organisations should consider adopting ICT to assist their employees in the management of these two domains. This could be done in two ways. First, organisations could implement a code of conduct or provide guidelines for eliminating the intrusive and excessive use of ICT, especially after working hours. Secondly, organisations could pilot or implement flexible working hours and possible telecommuting initiatives