The activation of memory B cells to generate high affinity antibody responses in vitro and in vivo

Immunological memory is the hallmark of the adaptive immune system. The humoral branch of the immunological memory is mediated by memory B-cells (mB). Memory B cells are marked by longevity, expression of antibodies with high affinity, and ability to generate robust antibody responses upon reencountering pathogens. However, requirements for the activation of mB cells and the induction of humoral memory responses are not well understood. This thesis examines the role of Toll-like receptors (TLRs) in mB activation using an immunized mouse model. TLRs are a family of receptors that recognize common molecular patterns of microbial pathogens and stimulate innate immune responses. Our study found that mouse mB expressed TLR9 and 4, and responded to their agonists in vitro by differentiating into high affinity IgG secreting plasma cells. However, TLR agonists alone were not sufficient to activate memory B cells in vivo. Antigen was required for the clonal expansion of antigen-specific memory B cells, the differentiation of mB cells to high affinity IgG secreting plasma cells, and the recall of high affinity antibody responses. The Ag- specific B cells that had not yet undergone isotype switching showed a relatively higher expression of TLR4 than memory B cells, which was reflected in a heightened response to its agonist, but in both cases of TLR4 and 9 yielded mostly low affinity IgM secreting plasma cells. When immunized together with the antigen, TLR agonists not only boosted the antigen-specific titers, but also increased affinity and isotype switching of the immunoglobulin. Thus, while TLR agonists alone are unable to activate mB in vivo, they can enhance humoral memory responses induced by the antigen

Economic Development, Legality, and the Transplant Effect

We analyze the determinants of effective legal institutions (legality) using data from 49 countries. We show that the way the law was initially transplanted and received is a more important determinant than the supply of law from a particular legal family. Countries that have developed legal orders internally, adapted the transplanted law, and/or had a population that was already familiar with basic principles of the transplanted law have more effective legality than countries that received foreign law without any similar pre-dispositions. The transplanting process has a strong indirect effect on economic development via its impact on legality.legal transplants, legal families, legality, effectiveness of legal institutions, economic development

Economic Development, Legality, and the Transplant Effect

We analyze the determinants of effective legal institutions (legality) using data from 49 countries. We show that the way the law was initially transplanted and received is a more important determinant than the supply of law from a particular legal family. Countries that have developed legal orders internally, adapted the transplanted law, and/or had a population that was already familiar with basic principles of the transplanted law have more effective legality than countries that received foreign law without any similar pre-dispositions. The transplanting process has a strong indirect effect on economic development via its impact on legality.transplant versus origin, receptive, unreceptive, direct and indirect transplants, legality

Phonon mediated conversion of exciton-polaritons Rabi oscillation into THz radiation

Semiconductor microcavities in the strong-coupling regime exhibit an energy scale in the THz frequency range, which is fixed by the Rabi splitting between the upper and lower exciton-polariton states. While this range can be tuned by several orders of magnitude using different excitonic medium, the transition between both polaritonic states is dipole forbidden. In this work we show that in Cadmium Telluride microcavities, the Rabi-oscillation driven THz radiation is actually active without the need for any change in the microcavity design. This feature results from the unique resonance condition which is achieved between the Rabi splitting and the phonon-polariton states, and leads to a giant enhancement of the second order nonlinearity.Comment: 6 pages, 2 figure

Familiensplitting der CDU/CSU: Hohe Kosten bei geringer Entlastung für einkommensschwache Familien

Die CDU/CSU schlägt in ihrem Wahlprogramm unter dem Stichwort Familiensplitting vor, das Kindergeld um 35 Euro pro Monat zu erhöhen und den Kinderfreibetrag auf die Höhe des Grundfreibetrags für Erwachsene anzuheben. Dies würde nach Berechnung des DIW Berlin Familien mit Kindern durchschnittlich um rund 700 Euro pro Jahr entlasten. Die Entlastung steigt mit dem Einkommen. Im untersten Zehntel (Dezil) der Einkommensverteilung beträgt die durchschnittliche Entlastung der Familien knapp 300 Euro pro Jahr, während sie im obersten Zehntel rund 840 Euro ausmacht. Familien mit geringen Einkommen werden also unterdurchschnittlich entlastet. Insgesamt kostet die Reform mehr als sieben Milliarden Euro pro Jahr. Im Zusammenhang mit der Familienbesteuerung wird häufig das französische Familiensplitting als Vorbild genannt. In dieser Studie werden der deutsche Familienleistungsausgleich sowie der Reformvorschlag der Union als Varianten eines Familienrealsplittings in Art und Wirkung mit dem tariflichen Familiensplitting in Frankreich verglichen. Es zeigt sich, dass schon das bestehende deutsche Modell in weiten Teilen großzügiger ist als das französische. Die finanziellen Vorteile für deutsche Familien würden sich bei Umsetzung der Unionspläne vergrößern. Generell haben alle Splittingmodelle den gravierenden Nachteil, dass sie dem familienpolitischen Ziel der Vereinbarkeit von Beruf und Familie entgegenwirken. Angesichts der hohen fiskalischen Kosten des Unionsvorschlags sollte deswegen in Erwägung gezogen werden, die Mittel eher in Maßnahmen zu investieren, die einen solchen Zielkonflikt nicht aufweisen, wie zum Beispiel den Ausbau qualitativ hochwertiger Kinderbetreuung.As part of their election manifesto, under the heading 'family income splitting', the German Christian Democratic Union/Christian Social Union of Bavaria (CDU/CSU) has proposed increasing child benefits by 35 euros per month and raising the tax-free allowance for dependent children to the same level as the basic personal tax exemption for adults. According to calculations by DIW Berlin, if this proposal were to be implemented, families with children would be around 700 euros a year better off, on average. The higher the family's income, the more tax relief they would receive. Families in the lowest income decile only stand to gain an average of just under 300 euros per year, while those in the upper decile will be approximately 840 euros per year better off. Consequently, tax relief for low-income families is below average and yet, the total cost of the reform is more than seven billion euros per annum. In the context of family taxation, the French family income splitting system is frequently cited as a model. The present study outlines the German family allowance system and also the reform proposed by the CDU/CSU as examples of 'real' family income splitting (Familienrealsplitting) and compares them, in terms of their structure and impact, with the French system of 'notional' family income splitting (tarifliches Familiensplitting). The analysis reveals that the current German model is already, to a great extent, more generous than the French one. Should they be implemented, the CDU/CSU plans would further increase the financial benefits already provided to German families under the current system. However, it is generally the case that all income splitting models have the serious disadvantage of undermining the important family policy goal of enabling a reconciliation of work and family life. Given the high fiscal costs of the CDU/CSU proposal, serious consideration should be given to investing the additional funds in other family policy measures that do not present conflicts of interest, such as expanding high-quality child care options, for example

Germination of Aspergillus fumigatus inside avian respiratory macrophages is associated with cytotoxicity

Although aspergillosis is one of the most common diseases in captive birds, the pathogenesis of avian aspergillosis is poorly known. We studied the role of avian respiratory macrophages as a first line of defense against avian aspergillosis. The phagocytic and killing capacities of avian respiratory macrophages were evaluated using pigeon respiratory macrophages that were inoculated with Aspergillus fumigatus conidia. On average, 25% of macrophage-associated conidia were phagocytosed after one hour. Sixteen percents of these cell-associated conidia were killed after 4 h and conidial germination was inhibited in more than 95% of the conidia. A. fumigatus conidia were shown to be cytotoxic to the macrophages. Intracellularly germinating conidia were located free in the cytoplasm of necrotic cells, as shown using transmission electron microscopy. These results suggest that avian respiratory macrophages may prevent early establishment of infection, unless the number of A. fumigatus conidia exceeds the macrophage killing capacity, leading to intracellular germination and colonization of the respiratory tract

Neurovascular coupling: a parallel implementation

A numerical model of neurovascular coupling (NVC) is presented based on neuronal activity coupled to vasodilation/contraction models via the astrocytic mediated perivascular K + and the smooth muscle cell (SMC) Ca2+ pathway termed a neurovascular unit (NVU). Luminal agonists acting on P2Y receptors on the endothelial cell (EC) surface provide a flux of inositol trisphosphate (IP3) into the endothelial cytosol. This concentration of IP3 is transported via gap junctions between EC and SMC providing a source of sacroplasmic derived Ca2+ in the SMC. The model is able to relate a neuronal input signal to the corresponding vessel reaction (contraction or dilation). A tissue slice consisting of blocks, each of which contain an NVU is connected to a space filling H-tree, simulating a perfusing arterial tree (vasculature) The model couples the NVUs to the vascular tree via a stretch mediated Ca2+ channel on both the EC and SMC. The SMC is induced to oscillate by increasing an agonist flux in the EC and hence increased IP3 induced Ca2+ from the SMC stores with the resulting calcium-induced calcium release (CICR) oscillation inhibiting NVC thereby relating blood flow to vessel contraction and dilation following neuronal activation. The coupling between the vasculature and the set of NVUs is relatively weak for the case with agonist induced where only the Ca2+ in cells inside the activated area becomes oscillatory however, the radii of vessels both inside and outside the activated area oscillate (albeit small for those outside). In addition the oscillation profile differs between coupled and decoupled states with the time required to refill the cytosol with decreasing Ca2+ and increasing frequency with coupling. The solution algorithm is shown to have excellent weak and strong scaling. Results have been generated for tissue slices containing up to 4096 blocks

Therapeutic opportunities for targeting cold pain pathways

Cold pain is a frequent symptom in neuropathic pain. Compared to other pain modalities, such as heat pain, the mechanisms behind physiological and pathological cold pain remain elusive. Moreover, it is becoming increasingly evident that cold pain pharmacology differs between various neuropathic pain conditions, making mechanism-directed treatment based on an understanding of the underlying pathophysiological mechanisms imperative to achieving clinical success. Here we review the processes of physiological and abnormal cold sensing, the pharmacology of cold nociception, cold hyperalgesia and cold allodynia, and provide an overview of cold pain syndromes and their current and potential treatments