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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.

Die Funktionsweise der FNTs ist trotz der großen pharmazeutischen Relevanz der auf sie angewiesenen Organismen bisher wenig erforscht und wurde bisher durch verschiedene, sich gegenseitig ausschließende Mechanismen erklärt. Während die eine Gruppe den für den Substrat-Proton-Symport nötigen Protonierungsschritt des Substrats einem zentralen Histidin im Transportpfad zuschreibt, wird im dielectric-slide-Mechanismus die Funktionsweise unabhängig von diesem Histidin erklärt. Hier wird konservierten Lysinen an den Transportpfadeingängen die wichtige Rolle der Substrat-Anion-Anziehung zugeschrieben. Um die korrekte Theorie des FNT-Mechanismus zu identifizieren wurden mit den beiden in der Natur vorkommenden FNTs EhFNT aus E. histolytica und BtFdhC1 aus B. thuringiensis erstmalig FNTs untersucht, die an der zentralen Position des Transportpfades statt des üblichen protonierbaren Histidins mit Asparagin (EhFNT) oder Glutamin (BtFdhC1) nicht protonierbare Aminosäuren tragen. Die Lysine an den Transportpfadeingängen sind dagegen vorhanden. Dabei wurde durch Streulichtmessungen an FNT-Liposomen festgestellt, dass beide Ziel-FNTs Monocarboxylate protonengradientenabhängig transportieren. Es konnte zudem gezeigt werden, dass sich die FNTs mit und ohne zentrales Histidin in Bezug auf Substratselektivität und -affinität ähneln. Durch diese Ergebnisse konnte gezeigt werden, dass nur der dielectric-slide-Mechanismus die Funktionsweise der FNTs korrekt wiedergibt. Da FNTs in Organismen den Import von Substraten oder den Export von metabolischen Endprodukten ermöglichen, sollte in dieser Arbeit auch die Direktionalität von FNTs untersucht werden. Dafür wurde der plasmodiale FNT PfFNT untersucht. Dieser ermöglicht bidirektionalen, Protonengradienten-abhängigen Substrattransport. Nach den aus dieser Arbeit gewonnenen Erkenntnissen funktionieren FNTs bidirektional nach dem dielectric-slide-Mechanismus. FNTs are hardly explored even though a variety of pharmaceutical relevant organisms are dependent on them. Their functional mechanism is explained by different mutually exclusive theories. One group identified a central histidine, located in the FNT transport path, as the key for substrate protonation. Another group postulated the “dielectric slide” mechanism which describes substrate protonation independently of the existence of a central histidine. Here the key amino acids are conserved lysines, located at the entrances of the transport path. To clarify which of the postulated mechanisms describes FNT substrate transport correctly two natural FNTs were investigated which carry nonprotonable amino acids instead of histidine in the central position. These FNTs were EhFNT from E. histolytica with a central asparagine, and BtFdhC1 from B. thuringiensis with a central glutamine. Each of them possesses lysines at the transport path entrances. Both investigated FNTs were reconstituted into liposomes and shown to be able to transport monocarboxylates in a proton gradient dependent manner. Furthermore, the substrate selectivity and affinity of FNTs with or without central histidine were proved to be similar. In consequence of these findings the “dielectric slide” mechanism was proved to describe FNT-mediated substrate transport correctly. Since FNTs enable import or export of substrates and metabolic end products, the second aim of this research was to investigate their directionality. It could be shown that the plasmodial FNT PfFNT is able to transport substrates bidirectionally and pH-dependently. The present results could prove that FNTs function bidirectionally in accordance with the “dielectric slide” mechanism.

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.

In this paper, we propose a structured peer-to-peer (P2P) distribution scheme based on Fast Fourier Transform (FFT) graphs. We build a peer-to-peer network that reproduces the FFT graph initially designed for hardware FFT codecs. This topology allows content delivery with a maximum diversity level for a minimum global complexity. The resulting FFTbased network is a structured architecture with an adapted network coding that brings flexibility upon content distribution and robustness upon the dynamic nature of the network. This structure can achieve optimal capacity in terms of content recovery while solving the problem of last remaining blocks, even for large networks., Comment: Submitted to ICC 2010

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.

Objetivos: Determinar los niveles de marcadores inflamatorios en pacientes con DM1, en comparación con controles sin DM1, y su relación con el perfil lipídico, el control metabólico y la duración de la diabetes. Métodos: Se seleccionaron 38 pacientes con DM1, sin complicaciones crónicas de la diabetes, 13 del Servicio de Endocrinología del I.A.H.U.L.A de Mérida y 25 de consultas Endocrinológicas del Táchira. Grupo control: 40 sujetos sin DM, ajustados por edad y sexo. Se obtuvieron datos demográficos y se realizó examen físico. Se calculó el índice de masa corporal (IMC). La glicemia, triglicéridos (Tg), colesterol total (Ct) y C-HDL se cuantificaron por métodos enzimáticos, la Hb A1c por turbidimetría, la proteína C reactiva (PCR) ultrasensible por quimioluminiscencia y el factor de necrosis tumoral alfa (TNFα) por inmunoensayo Resultados: La tensión arterial sistólica (TAS) estuvo más elevada en el grupo de estudio (DM1; p=0,017). El CHDL mostró niveles significativamente mayores en el grupo de diabéticos (p=0,0001) y no se observaron diferencias significativas en el resto de los lípidos. La PCR no fue diferente entre los grupos pero mostró una correlación significativa y positiva con los marcadores de adiposidad (IMC y cintura) (p=0,0001), las cifras de tensión arterial (p=0,002) y la duración de la diabetes (p=0,02). El FNTα se encontró significativamente más alto en los pacientes diabéticos tipo 1 y presentó una fuerte correlación positiva con la glicemia (p=0,0001) y débil con la TAS (p=0,01). Conclusiones: El nivel aumentado de FTNα en los niños diabéticos y las correlaciones positivas de este factor con la glicemia, así como de la PCR con la adiposidad, la tensión arterial y la duración de la DM1, sugieren una posible relación entre marcadores inflamatorios y DM1, sin embargo, se requieren estudios de seguimiento para determinar su importancia. Objective: To determine the levels of inflammatory markers in patients with DM1 compared to controls without DM1, and their relationship with lipid profile, metabolic control and duration of diabetes. Materials and Methods: We selected 38 patients from the Endocrinology Service of IAHULA, Mérida (n = 13) and Táchira endocrinologist consultations (n = 25) with DM1 without chronic complications of diabetes (Study Group). We selected 40 patients without diabetes mellitus, adjusted for age and sex to patients, who formed the control group. We used a questionnaire covering demographic data and physical examination. Then we calculated the body mass index and laboratory tests in serum were performed: glucose, triglycerides, total cholesterol, LDL-C, HDL-C, HbA1c, C-reactive protein (CRP) and tumour necrosis factor (TNFα). Results: There was no statistical difference between study and control groups regarding age, weight, height and body mass index (BMI). Systolic blood pressure (SBP) was higher in the study group (DM1; p=0.017). HDLC levels were significantly higher in the group of diabetic children (p=0.0001) and there were no significant differences in the other lipid. Levels CRP was not different between groups but showed a significant positive correlation with markers of adiposity (BMI and waist circumference) (p=0.0001), arterial blood pressure (p=0.002) and duration of diabetes (p=0.02). The FNTα was significantly higher in type 1 diabetic patients and showed a strong positive correlation with hyperglycemia (p=0.0001) and weak with SBP (p=0.01). Conclusions: FTNα increased levels in diabetic children and the positive correlations of this factor with glycemia, as well as PCR with adiposity, blood pressure and duration of DM1, suggest a possible relationship between inflammatory markers and DM1, however, follow-up studies are needed to determine its importance.

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.

This paper presents a new construction of Maximum-Distance Separable (MDS) Reed-Solomon erasure codes based on Fermat Number Transform (FNT). Thanks to FNT, these codes support practical coding and decoding algorithms with complexity O(n log n), where n is the number of symbols of a codeword. An open-source implementation shows that the encoding speed can reach 150Mbps for codes of length up to several 10,000s of symbols. These codes can be used as the basic component of the Information Dispersal Algorithm (IDA) system used in a several P2P systems., Comment: submitted in CCNC'10

International audience; The ”SoftWare Radio (SWR)” concept has become a topic of widespread interest for reconfigurable mobile architecture design. It is seen as the next evolutionary step in the mobile communications. In this context of SWR, a way to decrease the runtime of the software reconfiguration and to optimize the sharing between the software and the hardware of the execution platform called ”parametrization” was introduced. This technique is based on two approaches, the first one is called the Common Function approach, the second one is called the Common Operator approach. Being interested on the second parametrization technique, we propose in this paper a reconfigurable FFT (Fast Fourier Transform) operator. This operator can be reconfigured to switch from an operator dedicated to compute the FFT in the complex field (i.e for OFDM modulation or frequential equalization) to an operator which computes the FFT in the Galois Field in order to perform Reed-Solomon (RS) encoding and two steps of the decoding process.