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This presentation introduces the conceptual framework behind Biblia pauperum-Transcriptions, a browser-based viewer for manuscript transcriptions and digital facsimiles. This project has been under development by Ralf Möller, Stefan Thiemann, Malena Ratzke, and Hanna Wimmer, in the context of the research project Reframing Old Contents for New Readers in Late-Medieval German One-Volume Libraries (FNT08, formerly D09). The research for this presentation was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – EXC 2176 ‘Understanding Written Artefacts: Material, Interaction and Transmission in Manuscript Cultures’, project no. 390893796. The research was conducted within the scope of the Centre for the Study of Manuscript Cultures (CSMC) at Universität Hamburg.

A distinctive character of the mature intraerythrocytic form of the malaria parasite, Plasmodium falciparum, is a high glycolytic flow rate to fulfill its energetic requirements. This action produces two mole of lactic acid per mole of glucose as the anaerobic end product resulting in large quantities that need to be removed from the parasite cytosol. On its way out into the bloodstream lactate has to cross three different phospholipid bilayers, the parasite plasma membrane, the parasitophorous vacuole membrane and the red blood cell membrane. Although transport characteristics have been described for lactate in P. falciparum the molecular identity of the underlying permease(s) is still unknown. Here the discovery of a gene, PfFNT, responsible for the peptide that facilitates lactate transport over the parasite plasma membrane is described. It is a member of the formate nitrite transporter family (FNT) with high sequence similarities to microbial FNTs. For characterization of the protein a Saccharomyces cerevisiae knock out strain was employed that has lost the ability to transport monocarboxylates. Using this system PfFNT lactate/proton symport was found. This was confirmed by a direct proportionality of L-lactate transport to the prevailing pH gradient. Moreover when this gradient was abolished by proton decouplers, i.e. carbonylcyanide-3-chlorophenylhydrazone (CCCP) and 2,4-dinitrophenol (DNP), transport ceased. The PfFNT facilitated substrate pattern fits microbial FNTs, with acetate exhibiting the highest permeability followed by formate, L-lactate, D-lactate and pyruvate in decreasing order. The dicarboxylate malonate was excluded showing selectivity of monovalent anions over multivalent anions which is also a common feature shared by all FNTs discovered so far. The non-charged molecule glycerol, which is similar in size to lactate, was also excluded. Moreover facilitation features, such as transport rates and inhibition profile, match earlier findings from measurements performed in isolated living parasites in vitro hinting at a central position of PfFNT in parasite metabolism. For this the antiplasmodial compounds phloretin, furosemide, and cinnamate derivatives where tested revealing IC50 values around 1 mM. Inhibition requires a negative moiety though, since the uncharged cinnamamide had no effect. Notably the organomercurial p-chloromercuribenzene sulfonate (pCMBS), an inhibitor of human lactate transport, did not alter transport rates of PfFNT. This, taken together with the fact that there are no FNT homologs apparent in the human genome indicates PfFNT as a novel promising antimalarial drug target. Additionally PfFNT is the only transporter of the plasmodial glycolytic pathway for which structure information is available from crystals of homologous proteins predisposing it to further design of high affinity inhibitors. Ein herausragendes Merkmal des intraerythrozytären Malariaerregers, Plasmodium falciparum, ist eine hohe glykolytische Flussrate um seinen Energiebedarf zu decken. Bei diesem Vorgang werden aus einem Molekül Glukose zwei Moleküle Laktat gebildet, welches als metabolisches Endprodukt in hohen Mengen anfällt und aus dem parasitären Zytosol ausgeschleust werden muss. Auf seinem Weg ins Blut muss das Laktat drei Phospholipid Doppelmembranen überwinden, die parasitäre Plasmamembran, die parasitäre Vakuolen Membran und die Membran der Erythrozyten. Obwohl diese Transportprozesse in P. falciparum bereits beschrieben wurden, konnte die molekulare Identität der zugrunde liegenden Permease(n) bis jetzt nicht geklärt werden. In dieser Arbeit wurde das Gen, PfFNT, identifiziert das für das Peptid codiert, welches für die Laktatleitung über die Parasiten Membran verantwortlich ist. Es gehört zur Familie der Formiat Nitrit Transporter (FNT) und besitzt ähnliche Transporteigenschaften wie mikrobielle FNTs. Zur Charakterisierung des Proteins wurde ein Saccharomyces cerevisiae knock-out Stamm verwendet, welcher nicht dazu befähigt ist Monocarboxylate zu transportieren. In diesem System wurde gezeigt, dass PfFNT Laktat in Symport mit Protonen leitet. Dieses wurde durch eine direkt zum vorherrschenden pH-Wert proportionale Transportrate belegt. Zudem konnte der Transport gestoppt werden, indem der pH-Gradient durch Protonenentkoppler, wie Carbonylcyanid-3-chlorophenylhydrazon (CCCP) und 2,4-Dinitrophenol (DNP) zerstört wurde. Das durch PfFNT geleitete Subtratspektrum entspricht dem der bisher beschriebenen mikrobiellen FNTs. Dabei zeigt das Acetat Molekül die höchste Permeabilität, gefolgt von Formiat, L-Laktat, D-Laktat und Pyruvat in absteigender Reihenfolge. Das zweifach negativ geladene Malonat wurde nicht transportiert, was ebenfalls zu der Selektivität der bisher beschriebenen FNTs passt, die alle nur einfach geladene Anionen leiten. Das ungeladene Glycerol, welches eine ähnliche Größe zum Laktat Molekül aufweist, wurde ebenfalls nicht transportiert. Des Weiteren passen die Transporteigenschaften, wie Transportrate und Inhibitionsprofil zu denen, welche aus Daten gewonnen wurden, die in lebenden isolierten Parasiten in vitro gemessen wurden. Dieses deutet auf eine zentrale Rolle von PfFNT im parasitären Metabolismus hin. Hierfür wurden die antiplasmodial wirkenden Substanzen Phloretin, Furosemid und Zimtsäurederivate getestet, welche alle IC50 Werte um 1 mM zeigen. Inhibition erfordert zudem eine einzelne negative Ladung da das ungeladene Zimtsäureamid keine Wirkung auf die Transportrate hat. Bemerkenswert ist, dass die Organoquecksilber-Verbindung p-Chloromercuribenzensulfonat (pCMBS), ein bekannter Inhibitor des menschlichen Laktat Transports, den Transport durch PfFNT nicht verändert. Dies, zusammengenommen mit der Tatsache, dass es keine homologen Gene zu FNTs im menschlichen Genom gibt, deutet auf eine potentielle Rolle von PfFNT als neues Wirkstoffziel zur Behandlung von Malaria hin. Zusätzlich ist PfFNT der einzige Transporter des plasmodialen glykolytischen Stoffwechsels für den Strukturdaten aus Proteinkristallisationen in hoher Auflösung verfügbar sind. Daher ist PfFNT prädispositioniert für ein Design von hochaffinen Inhibitoren.

Tese de Doutoramento em Ciências Veterinárias. Especialidade de Ciências Biológicas e Biomédicas Coordination of reproductive events in the ovary and uterus demands the action of diverse factors as steroid hormones, eicosanoids, growth factors or cytokines on the regulating of processes such as angiogenesis, cell growth and differentiation, and apoptosis. Thus, the objectives of this study were to evaluate the influence of cytokines tumor necrosis factor α (TNF), interferon gamma (IFNG) and Fas Ligand (FASL) on the regulation of secretory function, angiogenesis, cell viability and apoptosis in the equine: (i) corpus luteum (CL) during luteal establishment and functional and structural regression; and (ii) endometrium during follicular phase (FP) and mid luteal phase (MLP), at cell, gene and molecular levels. All studied cytokine ligands and receptors were expressed in the equine CL, throughout the luteal phase, and in the endometrium, throughout the estrous cycle. During CL growth, TNF was shown to stimulate in vitro P4 and PGE2, to inhibit PGF2α secretion and to increase VEGF expression and angiogenic factors production. Thus, among all cytokines studied, TNF might give a luteotrophic contribution for CL establishment. Conversely, during CL regression, all cytokines alone reduced P4 and PGE2 secretion, while both FASL and TNF stimulated PGF2α secretion. TNF and IFNG reduced angiogenic factors secretion and FASL decreased VEGF expression. Cytokine association (TNF+IFNG+FASL) effectively promoted apoptosis and reduced luteal cell viability. Besides, they stimulated PGF2α and inhibited P4, PGE2 secretion and angiogenesis. In conclusion, cytokines interaction appears to coordinate functional and structural luteolysis in the mare. Concerning TNF role on endometrial cells, it can be concluded that during MLP, this cytokine stimulated PGE2 secretion, promoted angiogenic activity and NO secretion and increased endometrial cells viability. The interaction between TNF, oxytocin and steroid hormones was shown to be determinant for physiologic regulation of equine endometrium. RESUMO - Novas perspectivas na regulação imuno-endócrina da reprodução equina: estudos in vitro da função lútea e endometrial. - A coordenação da função reprodutora no ovário e no útero requer a participação de diversos factores como hormonas esteróides, eicosanóides, factores de crescimento ou citocinas, responsáveis por regular processos biológicos como a angiogénese, o crescimento e diferenciação celular e a apoptose. Assim, o presente estudo teve como objectivo avaliar a influência das citocinas factor de necrose tumoral α (FNT), interferão gama (IFNG) e Fas Ligando (FASL) na regulação da função secretora, angiogénese, viabilidade celular e apoptose: (i) no corpo lúteo (CL) durante o seu estabelecimento e regressão funcional e estrutural; e (ii) no endométrio durante as fases folicular (FF) e lútea média (FLM), a nível celular, molecular e genético na égua. A expressão de todos os ligandos e receptores das citocinas estudadas foi confirmada no CL, ao longo da fase lútea, e no endométrio, ao longo do ciclo éstrico. Durante o crescimento do CL, FNT estimulou a produção in vitro de P4 e PGE2, inibiu a secreção de PGF2α e aumentou a expressão de VEGF e a produção de factores angiogénicos. Desta forma, de todas as citocinas estudadas, FNT poderá contribuir como factor luteotrófico para o estabelecimento do CL. Contrariamente, aquando da regressão lútea, todas as citocinas individualmente reduziram a secreção de P4 e PGE2, enquanto FASL e FNT estimularam a secreção de PGF2α. FNT e IFNG inibiram a secreção de factores angiogénicos e FASL diminuiu a expressão de VEGF. A associação de citocinas FNT+IFNG+FASL promoveu de forma efectiva a apoptose e a redução da viabilidade das células lúteas. Além disso, estimulou a secreção de PGF2α e diminuiu as de P4 e PGE2, bem como inibiu a angiogénese. Concluindo, a interacção entre as várias citocinas parece coordenar a regressão funcional e estrutural do CL na égua. Considerando o papel do TNF nas células endometriais, conclui-se que, durante a FLM, este factor estimulou a secreção de PGE2, promoveu a produção de factores angiogénicos e de NO e aumentou a viabilidade das células endometriais. A interacção entre o FNT, a ocitocina e as hormonas esteróides provou ser determinante para a regulação fisiológica do endométrio equino.

International audience; Reed Solomon (RS) encoding/decoding in frequency domain is of significant interest in many wireless systems because the Fast Fourier Transform (FFT) operator is already present, at least in Orthogonal Frequency Division Multiplexing (OFDM) based ones. This paper presents and analyses the role of FFT to perform RS encoding/decoding in frequency domain. After explicating performance comparison, we propose to use RS codes defined over GF(Ft) instead of RS codes over GF(2m). Based on this proposition we have developed a common Dual Mode FFT (DMFFT) operator able to operate over two different domains C and GF(Ft). Various implementation strategies for DMFFT operator have been discussed. We emphasize that this DMFFT operator is a strong candidate for common operators in future air interface standards. We also explain our approach for designing flexible multistandard radio systems. Finally we incorporate the DMFFT operator in our graph and solve optimization problem by a heuristic based on simulated annealing.