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Principles of cognitive maps
(2021)
This thesis analyses the concept of a cognitive map in the research fields of geography. Cognitive mapping research is essential as it investigates the relations between cognitive maps and external representations of space that people regularly use by acquiring spatial knowledge, such as maps in geographic information systems. Moreover, cognitive maps, when expanded on semantic maps, explain the relations between people and things in a non-physically environment, where the considered space is not spanned by distance but with other non-spatially variables. Nevertheless, cognitive maps are often distorted. Although a good formation of a cognitive map is vital in navigation processes, cognitive distortions are barely investigated in the field of geography. By analyzing the relevant work, especially Tobler’s first law of geography, a new lexical variant of Tobler’s first law could be stated that could presumably describe a specific distortion in the processing of landmarks in cognitive maps.
The myrmecophilous Paederinae rove beetle genus Megastilicus Casey, 1889 from North America is reviewed based on museum specimens. Prior to this study, the genus was monotypic with one species Megastilicus formicarius Casey, 1889 described. Here, we provide a redescription of the genus and the type species, designate a lectotype, and provide pictures of habitus and illustrations of the aedeagus and genital segments. Additionally, we describe a new species for the genus, Megastilicus iowaensis sp. nov., include an identification key to the two species and present the distribution map of both of them, including new state records. We discuss the assignment of the genus to the subtribe Stilicina based on morphological features.
Standard biorelevant media reflect the average gastrointestinal (GI) physiology in healthy volunteers. The use of biorelevant media in in vitro experiments has become an important strategy to predict drug behaviour in vivo and is often combined with in silico tools in order to simulate drug plasma profiles over time. In addition to the healthy population, the effects of disease state or co-administration of other drugs on plasma profiles must be considered to assure drug efficacy and safety. Thus, there is a need for a more accurate representation of the human GI physiology when it is altered by disease or co-administered drugs in in vitro dissolution experiments.
This thesis focused on the development of biorelevant media and dissolution tests reflecting GI physiology in circumstances where the gastric pH is elevated. Diseases linked to an elevated gastric pH are hypochlorhydria and achlorhydria, but these days treatment with acid-reducing agents (ARAs) is the single greatest cause of elevation in gastric pH. pH-dependent drug-drug interactions (DDIs) with ARAs are frequent, as the ARAs are used in a number of diseases using a variety of drugs. As the drugs currently on the market are often poorly soluble and ionisable, their dissolution is highly dependent on the pH of the GI tract, especially the gastric pH.
The thesis research consisted of several steps. In the first step, physiological changes in the human GI tract during the therapy with ARAs were identified. Parameters of the standard biorelevant gastric medium FaSSGF were adjusted to the identified changes to reflect the impact of ARA co-administration on the gastric physiology. The media aim to assess the potential extent of the ARA impact on gastric physiology by introducing biorelevant media pairs, ARA pH 4 and pH 6 media, of which one reflects a lesser, and the other a stronger impact of ARAs.
In the second step these ARA media were implemented in in vitro dissolution set-ups.
The dissolution of poorly soluble ionisable drugs was assessed using one-stage, two-stage and transfer model set-ups, as well as using a more evolved in vitro system TIM-1. Comparison of results from dissolution set-ups using the standard, low pH, gastric biorelevant medium FaSSGF (pH 1.6 or 2), and the same set-ups using ARA pH 4 and pH 6 media, shows a decrease in dissolution rate and extent for weakly basic compounds PSWB 001 and dipyridamole, and an increase in rate and extent of dissolution for the weakly acidic compound raltegravir potassium, when the gastric pH is elevated. Due to different physicochemical properties, the extent of the impact of physiological changes during ARA therapy (when either ARA pH 4 or pH 6 medium is selected) on dissolution varied among the model drugs. Thus, the bracketing approach, which considers a range of the possible ARA co-administration impact on drug dissolution, was confirmed to be best practice in assessing the impact of ARAs.
In the third step, dissolution data from in vitro experiments with ARA media was implemented into in silico models. The predictions using various in silico model approaches in Simcyp™ Simulator (minimal and full PBPK model, dissolution input using DRM and DLM) successfully bracketed in vivo data on drug administration during ARA therapy and correctly predicted an overall decrease in plasma concentration for the two model weakly basic compounds and an increase in plasma concertation for the model weakly acidic compound.
In all assessed scenarios, the ARA methods proved to be an essential part of evaluating and predicting the impact of ARAs on drug pharmacokinetics, and appropriately predicted the extent of a possible impact of ARAs on the drug plasma profiles. Thus, the ARA biorelevant media and dissolution tests were demonstrated to be valuable tools reflecting administration of drugs when the gastric pH is elevated and able to predict the impact of ARA therapy on drug administration.
The ability to evaluate the impact of human (patho) physioloy on drug behaviour in the gastrointestinal tract is of great importance, as the GI conditions play a significant role in drug release and absorption. Thus, there is great interest on the part of the pharmaceutical industry and regulatory agencies to develop best practices in this field, especially for pH-dependent DDIs. The media and dissolution tests developed in this thesis are biorelevant methods appropriate for evaluation of the impact of elevated gastric pH on drug efficacy and safety. Such methods, used as a risk assessment tool, in connection with evaluation of the efficacy window and potential toxicity, may help to increase confidence about decisions as to whether a pH-effect will occur and whether it is relevant or not, prior to conducting clinical studies. They may also enable changes in inclusion/exclusion criteria during recruiting for large-scale efficacy trials. In fact, the biopharmaceutic approach to drug development is becoming standard practice on a number of fronts, including metabolic DDIs, renal and hepatic insufficiency, powering decision-making process and possibly even waiving certain types of clinical studies.
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Selizitapia gen. nov. (Hemiptera: Fulgoromorpha: Flatidae) from tapia woodlands of Madagascar
(2021)
A new monotypic genus of flatid planthoppers (Hemiptera: Fulgoromorpha: Flatidae), Selizitapia gen. nov., is described for Selizitapia pennyi gen. et sp. nov. (type species) from the island of Madagascar. Habitus, male and female external and internal genital structures of the new species are illustrated and compared with similar taxa. Selizitapia pennyi gen. et sp. nov. is endemic to Madagascar where it is known to date only from one locality in the Central Plateau and is associated with tapia woodland formation.
Resistant microbes are a growing concern. It was estimated that about 33,000 of people die because of the infections caused by multidrug resistant bacteria each year in Europe (ECDC, 2018, https://www.ecdc.europa.eu/). Bacteria can acquire resistance against toxic compounds via different mechanisms and intrinsic active efflux is one of the first mechanisms deployed by bacterial cells. The membrane-localized efflux pumps catalysing this reaction, extract toxic compounds from the interior of the cell and transport these to the outside, thereby maintaining sub-lethal toxin levels in the cytoplasm, periplasm and membranes. Gram-negative three-component efflux pumps, analysed in this study, are composed of an inner membrane protein, a member of the Resistance-Nodulation cell Division (RND) superfamily, an Outer Membrane Factor (OMF) protein and a Membrane Fusion Protein (MFP) that connects the two afore mentioned components into an active efflux pump. The pumps described in this work, AcrAB-TolC and EmrAB-TolC, are drug efflux pumps belonging to the RND and MFS superfamilies, respectively, while CusCBA is an efflux pump that belongs to the RND heavy metal efflux family. Another efflux pump that was used as a model for the design of an in vitro assay for the silver ion transport studies, CopA, belongs to the P-type ATPase superfamily. All pumps analysed in this study are part of the resistance system of Escherichia coli, which is a highly clinically relevant pathogen.
In order to examine the AcrAB-TolC, CopA and CusA efflux pumps, the individual components were separately produced in E. coli, purified to monodispersity and reconstituted in large unilamellar vesicles, LUVs. Means for the optimized production and adequate conditions for efficient reconstitution were presented in this study. The activity of AcrB in LUVs was detected using fluorescence quenching of the dye 8-hydroxy-1,3,6 pyrenetrisulfonate (pyranine), which is incorporated inside the proteoliposomes and is sensitive to the pH changes in its surrounding. The inactive AcrB variant with a substitution in the proton relay network, D407N, showed no activity in proteoliposomes, which correlates with the measurements done in empty liposomes. When AcrA was co-reconstituted with AcrB D407N proteoliposomes it did not restore protein activity. To test the assembly of the AcrAB-TolC pump out of its single components, an in vitro assay was established where the complex assembly was tested with AcrAB- and TolC-containing liposomes. These experiments showed putative AcrAB-TolC formation in the presence or absence of a pump substrate, taurocholate, as well as in the presence of the pump inhibitor, MBX3132. The assembly appeared stable over time and results were invariant in the presence or absence of a pH gradient across the AcrAB-containing membrane.
After determination of the ATPase activity of the P-type ATPase, CopA, in detergent micelles, the protein was reconstituted in LUVs. Quenching of the Ag+-sensitive dye Phen Green SK (PGSK), present on the inside of the CopA-containing proteoliposomes, was observed in presence of ATP and Ag+. Under the same conditions, but in absence of Ag+-ions, quenching was reduced by 80 % after 300 seconds. No PGSK-quenching was observed in control liposomes in the presence of ATP and Ag+. The additional presence of sodium azide led to minimal reduction of the PGSK-quenching as expected since sodium azide is not an inhibitor of P-type ATPases, but the quenching rate was similar to that of the same experimental condition with control liposomes.
The RND superfamily member CusA, as part of the tripartite CusCBA efflux pump, has been proposed to sequester Ag+ or Cu+ from either the cytoplasmic or periplasmic side of the inner membrane. The periplasmic transport of silver ions was implied from an in vitro assay where the quenching of a pH sensitive dye, 9-amino-6-chloro-2-methoxyacridine (ACMA), indicates acidification of the lumen of the proteoliposomes containing CusA when an inwardly directed pH was imposed. The same experiment with the CusA D405N variant, which was previously reported to be an inactive variant, also led to ACMA quenching, although at a slightly lower rate. Under application of an inwardly directed pH and a (negative inside), CusA-containing proteoliposomes showed a strong quenching of the incorporated PGSK dye, suggesting strong Ag+ influx.
The Major Facilitator Superfamily-(MFS-) type EmrAB-TolC pump has an analogous structural setup as the RND-type AcrAB-TolC pump. To examine the efflux of one of its substrates, carbonyl - cyanide m-chlorophenylhydrazone (CCCP), a plate-based susceptibility assay was used. The presence of the EmrAB-TolC pump confers lower susceptibility levels towards CCCP in E. coli, compared to cells not expressing the pump or cells expressing only the MFS component, indicating that EmrAB-TolC extrudes CCCP.
The work done in this study opens up a path towards investigation of drug and metal resistance in vitro. The methodologies to obtain proteoliposomal samples of multicomponent efflux pumps and subsequent measurements of drug/metal ion and H+ fluxes, as well as the determination of pump assembly are crucial for the future research on pump catalysis and transport kinetics. The in vivo drug-plate assays done in this work provide initial insights for future investigations of the drug susceptibility of E. coli expressing the MFS-type tripartite efflux pumps.
Terahertz (THz) technology is an emerging field that considers the radiation between microwave and far-infrared regions where the electronic and photonic technologies merge. THz generation and THz sensing technologies should fill the gap between photonics and electronics which is defined as a region where THz generation power and THz sensing capabilities are at a low technology readiness level (TRL). As one of the options for THz detection technology, field-effect transistors with integrated antennae were suggested to be used as THz detectors in the 1990s by M. Dyakonov and M. Shur from where the development of field-effect transistor-based detector began. In this work, various FET technologies are presented, such as CMOS, AlGaN/GaN, and graphene-based material systems and their further sensitivity enhancement in order to reach the performance of well-developed Schottky diode-based THz sensing technology. Here presented FET-based detectors were explored in a wide frequency range from 0.1 THz up to 5 THz in narrowband and broadband configurations.
For proper implementation of THz detectors, the well-defined characterization is of high importance. Therefore, this work overviews the characterization methods, establishes various definitions of detector parameters, and summarizes the state-of-the-art THz detectors. The electrical, optical, and cryogenic characterization techniques are also presented here, as well as the best results obtained by the development of the characterization methods, namely graphene FET stabilization, low-power THz source characterization for detector calibration, and technology development for cryogenic detection.
Following the discussion about the detector characterization, a wide range of THz applications, which were tested during the last four years of Ph.D. and conducted under the ITN CELTA project from HORIZON2020 program, are presented in this work. The studies began with spectroscopy applications and imaging and later developed towards hyperspectral imaging and even passive imaging of human body THz radiation. As various options for THz applications, single-pixel detectors as well as multi-pixel arrays are also covered in this work.
The conducted research shows that FET-based detectors can be used for spectroscopy applications or be easily adapted for the relevant frequency range. State-of-the-art detectors considered in this work reach the resonant performance below 20 pW/√Hz at 0.3 THz and 0.5 THz, as well as 404 pW/√Hz cross-sectional NEP at 4.75 THz. The broadband detectors show NEP as low as 25 pW/√Hz at around 0.6 THz for the best AlGaN/GaN design and 25 pW/√Hz around 1 THz for the best CMOS design. As one of the most promising applications, metamaterial characterization was tested using the most sensitive devices. Furthermore, one of the single-pixel devices and a multi-pixel array were tested as an engineering solution for a radio astronomy system called GREAT in a stratosphere observatory named SOFIA. The exploration of the autocorrelation technique using FET-based devices shows the opportunity to employ such detectors for direct detection of THz pulses without an interferometric measurement setup.
This work also considers imaging applications, which include near-field and far-field visualization solutions. A considerable milestone for the theory of FET technology was achieved when scanning near-field microscopy led to the visualization of plasma (or carrier density) waves in a graphene FET channel. Whereas another important milestone for the THz technology was achieved when a 3D scan of a mobile phone was performed under the far-field imaging mode. Even though the imaging was done through the phone’s plastic cover, the image displayed high accuracy and good feature recognition of the smartphone, inching the FET-based detector technology ever so close to practical security applications. In parallel, the multi-pixel array testing was carried out on 6x7 pixel arrays that have been implemented in configurable-size aperture and imaging configurations. The configurable aperture size allowed the easier detector focusing procedure and a better fit for the beam size of the incident radiation. The imaging has been tested on various THz sources and compared to the TeraSense 16x16 pixel array. The experimental results show the big advantage of the developed multi-pixel array against the used commercial technology.
Furthermore, two ultra-low-power applications have been successfully tested. The application on hyper-frequency THz imaging tested in the specially developed dual frequency comb and our detector system for 300 GHz radiation with 9 spectral lines led to outstanding imaging results on various materials. The passive imaging of human body radiation was conducted using the most sensitive broadband CMOS detector with a log-spiral antenna working in the 0.1 – 1.5 THz range and reaching the optical NEP of 42 pW/√Hz. The NETD of this device reaches 2.1 K and overcomes the performance limit of passive room-temperature imaging of the human body radiation, which was less than 10 K above the room temperature. This experiment opened a completely new field that was explored before only by the multiplier chain-based or thermal detectors.
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Ćurčić, Srećko ; Pavićević, Dragan ; Vesović, Nikola ; Vrbica, Maja ; Kuraica, Miloš ; Marković, Đorđe ; Petković, Matija ; Lazović, Vladimir ; Pantelić, Dejan ; Bosco, Fabrizio
Three subterranean leptodirine leiodid taxa, viz., Bozidaria Ćurčić & Pavićević gen. nov., Bozidaria serbooccidentalis Ćurčić & Pavićević gen. et sp. nov. and Proleonhardella (Proleonhardella) tarensis Ćurčić & Pavićević sp. nov., are described and diagnosed. Bozidaria Ćurčić & Pavićević gen. nov. belongs to the phyletic series of “Leonhardella”. The new beetle taxa differ from their closest relatives in numerous morphological characters. They most likely belong to phyletic lineages of Pliocene age. The new leiodid taxa are endemic to the Dinaric mountain chain of western Serbia. Keys to the leptodirine leiodid genera of the phyletic series of “Leonhardella” and to the taxa of the genus Proleonhardella Jeannel, 1910 are included.
Dieser Beitrag beschäftigt sich mit sprachbezogenen Witzen und ihrem konkreten Einsatz im Deutsch als Fremdsprachenunterricht. Der Fokus dieses Beitrags liegt auf der Empfehlung von Anwendungsbeispielen für die Nutzung von sprachbezogenen Witzen im DaF-Unterricht, die das vorrangige Ziel der Beschäftigung mit Stereotypen und der Entwicklung einer interkulturellen Kompetenz anstreben. Hierzu wird vorerst klargestellt was mit dem Begriff Witz gemeint wird, insbesondere, was als "sprachbezogener Witz" in der Studie angesehen wird. Im Nachhinein wird auf die Bedeutung des Einsatzes von Witzen im Fremdsprachenunterricht eingegangen, sodass der Bedarf und Grund für die Anwendung dargelegt werden kann. Zur Lieferung adäquater Antworten auf die Forschungsfragen soll der Forschungsstand beschrieben werden und im praktischen Teil sollen Witze aus verschiedenen online Quellen ausgesucht und bewertet werden, die das Thema "Sprache" vorweisen. Die Witze wurden zum Schluss als jeweils ein Didaktisierungsvorschlag erarbeitet. Mit den Didaktisierungsvorschlägen wurde aufgezeigt, dass sprachbezogene Witze sich für die Entwicklung einer interkulturellen Kompetenz, durch die Beschäftigung mit Stereotypen und Vorurteilen im DaF-Unterricht, sehr gut eignen können. Die Didaktisierungsvorschläge wurden nach dem Modell "Didaktische Analyse" erstellt.
Bu çalışmada Turizm Fakültesi öğrencilerinin seçmeli yabancı dil derslerine (Almanca, Fransızca ve İtalyanca) yönelik kaygı düzeylerinin çeşitli değişkenlere göre incelenmesi amaçlanmaktadır. Araştırmada nicel araştırma yöntemlerinden tarama modeli kullanılmıştır. Araştırmanın evrenini Türkiye'de Turizm Fakültelerinde eğitim alan öğrenciler oluşturmaktadır. Araştırmanın örneklemini ise bir devlet üniversitesinin Turizm Fakültesinde eğitim alan ikinci, üçüncü ve dördüncü sınıf öğrencileri oluşturmaktadır. Araştırmaya toplam 141 öğrenci katılmıştır. Katılımcıların %46,1'i kadın, %53,9'u ise erkektir. Çalışmada veri toplama araçları olarak araştırmacı tarafından oluşturulan kişisel bilgi formu ile Horwitz, Horwitz ve Cope (1986) tarafından geliştirilmiş "yabancı dil dersi kaygı ölçeği" kullanılmıştır. Ölçek 33 madde ve 3 alt boyuttan oluşmaktadır. Araştırmada yer alan verilerin analizinde SPSS 22 paket programı kullanılmıştır. Örnekleme ait istatistikler frekans analiz ile hesaplanmıştır. Bağımsız değişkenlerin hesaplanmasında t-testi ve tek yönlü varyans analizi (ANOVA) testleri kullanılmıştır. Tüm hesaplamalarda anlamlılık düzeyi p<,05 olarak kabul edilmiştir. Araştırmanın sonucunda, “dil dersinde konuşma kaygısı” boyutunda erkek öğrencilerin kadın öğrencilere göre daha kaygılı oldukları; eğitim alınan bölüm değişkenine bağlı olarak "dil dersine yönelik ilgi" ve "yabancılarla konuşma kaygısı" boyutlarında anlamlı bir şekilde farklılaştığı; eğitim alınan sınıf düzeyi değişkenine göre herhangi bir farka rastlanmadığı; seçilen yabancı dil değişkenine bağlı olarak yalnızca "yabancılarla konuşma kaygısı" boyutunda anlamlı şekilde farklılaştığı; başarı durumu değişkenine göre bir farka rastlanmadığı ve mezuniyet sonrası plan değişkenine bağlı olarak ise yalnızca "dil dersinde konuşma kaygısı" boyutunda anlamlı farklılık gösterdiği ortaya konmuştur.
"Öğrenci Törless'in bunalımları" : 20. yüzyıl başındaki eğitim sorunsalı ve Hitler'in ayak sesleri
(2021)
Robert Musil (1880-1942), modern roman türünün oluşumuna ve gelişimine önemli katkıları olan, 20. yüzyılda Avusturya Edebiyatı'nın en önde gelen yazarlarındandır. Eserlerinde 20. yüzyıl başındaki dönüşümü ve bu dönüşümün birey ve toplum üzerindeki etkilerini konu edinmektedir. 1906 yılında yayınlanan ilk romanı "Öğrenci Törless'in Bunalımları'nda" da içinde yaşanılan dönemin ve sınıf farkının eğitime yansıması, eğitim ve yatılı okul sisteminin insanlıkla bağdaşmayan yanları, buna bağlı olarak genç ve yaratıcı bireylerin sorunları ve otonom gelişimlerinin engellenmesi gibi konular ele alınmıştır. Ayrıca eserde yüzyıl başındaki dönüşüme paralel olarak toplumda yavaş yavaş hissedilmeye başlanan faşizmin ayak sesleri konu edinilmiştir. Bu çalışmada, 20. yüzyıl başındaki modernist dönüşümün eğitim ve okul sistemi üzerindeki izleri gün ışığına çıkarılmaya ve Hitler ekolünün alttan alta gelişi gösterilmeye çalışılmıştır. Bu vesileyle çalışmamızın özellikle o dönemdeki eğitim sorunsalı ve Hitler zihniyetinin doğuşu üzerine yapılacak çalışmalara bir rehber olması amaçlanmıştır. Araştırma sürecinde metne bağlı, yorum bilimine dayalı inceleme yöntemlerine ve yer yer de metinlerarasılık yöntemine başvurulmuştur.