Rebate Rules in Reward-Based Crowdfunding: Introducing the Bid-Cap Rule

We study the efficacy of rebate rules in reward-based crowdfunding, where a project is only realized when a funding goal is met, and only those who pledge at least a reservation price receive a reward from the project. We propose and experimentally test two rebate rules against the customary all-or-nothing model. Firstly, we adapt the proportional rebate rule from threshold public good games to our reward-based setting. Secondly, we develop the novel bid-cap rule. Here, pledges must only be paid up to a cap, which is determined ex-post such that the provision point is exactly met. Theoretically, the bid-cap rule induces weakly less variance in payments compared with the proportional rebate rule. In our experiment, we find that both rebate rules induce higher pledges and increase the project realization rate in comparison to the all-or-nothing model. Further, we can confirm that the variance of payments is lower under the bid-cap rule compared with the proportional rebate rule

Ground beetles as indicator species for stand tradition and nearness to nature of broadleaved forests

Laufkäfer werden in ökologischen Studien zur Lebensraumbewertung sehr häufig als Bioindikatoren hinzugezogen (PLATEN & KOWARIK 1995, PLATNER et al. 1996, POSPISCHIL 1981), denn ihre Ökologie und die daraus resultierenden ökologischen Ansprüche sind durch zahlreiche Studien eingehend untersucht (u.a. BAEHR 1980, LINDROTH 1945, THIELE 1977). Unterschiede in der Artengemeinschaft bzw. Änderungen in der Abundanz der Carabiden lassen Rückschlüsse über Habitatqualität, Standortsfaktoren, Minimalareal- Fragen, Habitattradition und Vernetzung von Lebensräumen zu. Diese Tatsachen wurden ausgenutzt, um die Bestandstradition und die Naturnähe der Bestockung der Probeflächen zu untersuchen. Diese sind weitgehend naturnahe Wälder im südbayerischen Tertiärhügelland, einem insgesamt wenig naturnahen, forstlich durch Fichtenforste geprägten Landschaftsraum.The role of isolated near natural broadleaved forests in a landscape dominated by manmade coniferous plantations was investigated using ground beetles (Coleoptera: Carabidae) as indicator species. Natural beech and ravine forests as well as near-natural secondary oak forests, and a pure spruce stand were researched using pitfall traps. The results were ordinated using CCA including 76 additional sites in similar forest associations. The carabid faunas of these associations group together rather well. Wet forests are most distinct, including natural oak-hornbeam forests and wet ravine forests. Dry ravine forests on calcareous slopes overlap with beech forests on calcareous sites to a certain degree, while acidic beech forests are distinct. The investigated isolated sites do not group with the natural reference sites well, the main reason being „size of forest“ and „size of broadleaved forest“, according to the CCA. These factors are to blame for an apparent loss of species that could be expected for these sites according to data from similar sites under different circumstances. Especially one investigation area with only about 5 hectares of completely isolated forest and a historical record of large-scale deforestation (for use as a vineyard and as a coppice-with-standards stand) is deprived of many species. In the other investigated area, Carabus purpurascens, absent from the entire tertiary hill land of southern Bavaria, was rediscovered after approximately 100 years in an oak forest. In this site, circumstances are apparently better, albeit not good, again due largely to habitat fragmentation, though not habitat tradition. The species lost on these sites are foremost stenotopic forest species with preference to broadleaved forests, species with a montane distribution and large species (several species of the genus Carabus) with accordingly large requirements for contiguous habitat. The results stress the importance of the protection of forests with a habitat tradition on a sufficient area

Comparison of the canopy fauna of silver fir (Abies alba) and spruce trees (Picea abies)

Natürlicherweise war die Tanne (Abies alba) in den bayerischen Wäldern mit Anteilen von bis zu 20% vertreten (nach ROTHE & BORCHERT 2003). Seit 150 Jahren aber gehen die Tannenbestände in drastischem Ausmaß zurück, was nicht nur auf die wachsende Schadstoffbelastung der Luft, sondern auch auf hohe Wildbestände und die einseitige Waldbewirtschaftung zugunsten der Fichte (Picea abies) zurückzuführen ist. In jüngster Zeit wird seitens der Staatsforstverwaltung angestrebt, der Tanne ihren angestammten Platz in unseren Wäldern wieder einzuräumen (BAYERISCHES STAATSMINISTERIUM FÜR LANDWIRTSCHAFT UND FORSTEN 1993). Es stellt sich die Frage, welchen Beitrag die Tanne zur Biodiversität in Wäldern und speziell in Mischwäldern leistet. Frühere Untersuchungen beschrieben die Tannenfauna als artenarm im Vergleich mit anderen Baumarten (BÖHME 2001, BUCKING 1998), allerdings wurde die Kronenfauna dabei stets vernachlässigt. Da aber 90% eines Hochwaldes über der Reichhöhe eines Menschen liegt (BUßLER et al. 2004), sind Untersuchungen im Kronenraum höheren Straten für eine umfassende Aussage über die Fauna auf Bäumen von großer Bedeutung. Bis jetzt gibt es trotz des generell wachsenden Interesses an der Kronenfauna keine umfassenden Untersuchungen an Tanne (MÜLLER & GOSSNER 2004). Mit dem hier vorgestellten Projekt sollte begonnen werden, die Wissenslücke um die Insektenfauna in Tannenkronen zu schließen. Den xylobionten Käfern galt besondere Aufmerksamkeit, da sie als eine baumartengebundene Insektengruppe für vergleichendeUntersuchungen sehr gut geeignet und sowohl taxonomisch als auch ökologisch gut untersucht sind. Daneben wurden Heteroptera, Neuropterida und Hymenoptera bearbeitet .In the context of forest ecological support programs of silver fir as the “Tree of the year 2004”, the relative contribution of fir and spruce trees to forest insect diversity is compared in present investigation. Previous studies had postulated a species poor community on fir. Insects were sampled by flight-interception traps at 6 different sites in Bavaria in the year 2004. Traps were installed in the centre of the canopy of a total of 30 trees (>100 years) of each species and emptied monthly from April through October. Specimens of Coleoptera, Hymenoptera, Heteroptera and Neuropterida were enumerated. A total of 20.562 specimens was collected, with Coleoptera being the dominant order. The comparison between fir and spruce revealed significant differences in numbers of specimens of Hymenoptera, Heteroptera and Neuropterida. Regarding saproxylic beetle species, a significant difference between fir and spruce was found at one site (Feuchtwangen) only. The Sørensen index values showed a strong similarity between the mountainous sites (Inzell, Reit im Winkel, Nationalpark Bayerischer Wald). Several species in the samples are listed in the German Red Data Book of endangered and threatened species. Most of these were sampled on fir, e.g. Episernus striatellus (RL-D 0) and Euglenes pygmaeus (RL-D 1)

Customer Loyalty Programs and Privacy Concerns

In recent years, loyalty programs have been established allowing the creation of detailed consumer profiles by collecting and processing purchase information. Collecting this information, however, raises privacy concerns of customers. In this work, we provide the results of an empirical study which reveal that privacy concerns have an impact on the probability of participating in loyalty programs. We identify a privacy-sensitive segment of customers using demographic and psychographic data that, in principle, would participate in a loyalty program, however, refrains from doing so because of privacy concerns. Moreover, we found that people participating in customer loyalty programs are more concerned about their privacy than non-participants, which is an interesting though counterintuitive result

On the assembly of the leukotriene biosynthetic complex in intact cells and its pharmacological inhibition

Leukotrienes (LT) are potent lipid mediators derived from arachidonic acid (AA) via the 5-LO pathway [1]. AA is converted to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HPETE), which in turn is metabolized to LTA4. In the cell, 5-LO activity depends on a crucial translocation from the soluble compartment to the nuclear membrane-bound 5-lipoxygenase-activating protein (FLAP) to achieve endogenously released AA as substrate for LT biosynthesis [2]. Although 5-LO and LT biosynthesis is known for more than 35 years, a role in the development of cardiovascular diseases (CVD), cancer, and Alzheimer`s disease besides chronic allergic diseases like asthma has only recently been discovered [3]. Inspired by the therapeutic potential, BRP-7 was identified as a new class of FLAP inhibitors with high efficacy to inhibit LT biosynthesis in vitro and in vivo. Additionally, a powerful mammalian stable expression system of 5-LO and FLAP in HEK293 cells was established to clearly determine putative FLAP inhibitors and study FLAPs undisputed significance for cellular LT biosynthesis. FLAP increases cellular 5-LO product formation by enhancing the LTA4 synthase activity, and supports 5-LO membrane accumulation. For the first time, we provide strong evidence for an effective in situ interaction of native 5-LO and FLAP at the nuclear membrane in primary human leukocytes and stable transfected HEK293 cells by proximity ligation assay (PLA). 5-LO/FLAP interaction occurs delayed to 5-LO activity and translocation. FLAP antagonists prevent the 5-LO/FLAP interaction, and AA and/or 5-HPETE function as regulating molecules for the 5-LO/FLAP complex assembly

Diversity of aphidophagous insects in the Bavarian Forest : what contributions does White fir make in comparison to spruce?

Die Weißtanne (Abies alba) – Symbol für naturnahe Waldwirtschaft – ist im Bayerischen Wald beheimatet. Die Tanne ist dort neben Fichte und Buche das prägende Element der Bergmischwälder auf Höhen von 600 bis 1250 m. Einstmals war sie mit etwa 20 % (ROTHE & BORCHERT 2003) am Waldaufbau beteiligt. Seit rund 150 Jahren ist jedoch ein drastischer Rückgang der Tanne - nicht nur im Bayerischen Wald – zu verzeichnen. Die Ursachen für den Rückgang der Tanne sind überwiegend anthropogen bedingt. In erster Linie ist hier die Forstwirtschaft zu erwähnen, die bestrebt ist durch waldbauliche Maßnahmen den Fichtenanteil anzuheben. An zweiter Stelle stehen die neuartigen Waldschäden, welche, bedingt durch Schadstoffimmissionen in den 70er und 80er Jahren des letzten Jahrhunderts, zu verstärktem Absterben der Tanne führten. Noch heute ist die Tanne die am stärksten geschädigte Baumart in Bayern (BAYSTMLF 2002). Ein weiterer nicht zu vergessender Faktor für den Rückgang der Tanne sind die z.T. hohen Wildbestände, durch deren Verbiss und Schälen junger Tannen das Heranwachsen einer neuen Generation verhindert wird. Mit dem Rückgang der Tanne verändert sich jedoch nicht nur die Baumartenzusammensetzung, sondern auch Tier- und Pflanzenarten sind direkt und indirekt betroffen. Die Arthropodenfauna der bisher kaum untersuchten Tanne wird als relativ artenarm beschrieben (BRÄNDLE & BRANDL 2001), jedoch gibt es wenige spezielle Untersuchungen an dieser Baumart (MÜLLER & GOßNER 2004).In the present study the impact of White fir (Abies alba) as compared to spruce (Picea abies) on the diversity of aphidophagous insects was analysed. To this end, tree crown communities of five trees each were sampled by flight interception traps in the Bavarian Forest National Park in the year 2004. Altogether 386 specimens of 31 aphidophagous species, including: Heteroptera, Neuropterida, and Coccinellidae (Coleoptera) were captured on the two coniferous species. Number of specimens and species as well as diversity (Fisher’s alpha) of aphidophagous insects was significantly higher on White fir as compared to spruce. With the exception of three species, all species where found in higher numbers in tree crowns of White fir. The favourable microclimatic conditions of the more open crown structure of White fir compared to spruce as well as the quality and quantity of aphid resource availability are discussed as possible abiotic and biotic factors affecting the observed patterns of aphidophagous communities

5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation

© FASEB. Leukotrienes (LTs) are proinflammatory lipid mediators formed from arachidonic acid in a 2-step reaction catalyzed by 5-lipoxygenase (5-LOX) requiring the formation of 5-HPETE [5(S)-hydroperoxy-6-trans-8,11,14-ciseicosatetraenoic acid] and its subsequent transformation to LTA4 . 5-LOX is thought to receive arachidonic acid from the nuclear membrane-embedded 5-LOX-activating protein (FLAP). The crystal structure of 5-LOX revealed an active site concealed by F177 and Y181 (FY cork). We examined the influence of the FY cork on 5-LOX activity and membrane binding in HEK293 cells in the absence and presence of FLAP. Uncapping the 5-LOX active site by mutation of F177 and/or Y181 to alanine (5-LOX-F177A, 5-LOX-Y181A, 5-LOX-F177/Y181A) resulted in delayed and diminished 5-LOX membrane association in A23187-stimulated cells. For 5-LOX-F177A and 5-LOX-F177/Y181A, formation of 5-LOX products was dramatically reduced relative to 5-LOX-wild type (wt). Strikingly, coexpression of FLAP in A23187-activated HEK293 cells effectively restored formation of 5-H(p)ETE (5-hydroxy- and 5-peroxy-6-trans-8,11,14-cis-eicosatetraenoic acid) by these same 5-LOX mutants (≈60-70% 5-LOX-wt levels) but not of LTA4 hydrolysis products. Yet 5-LOX-Y181A generated 5-H(p)ETE at levels comparable to 5-LOX-wt but reduced LTA4 hydrolysis products. Coexpression of FLAP partially restored LTA4 hydrolysis product formation by 5-LOX-Y181A. Together, the data suggest that the concealed FY cork impacts membrane association and that FLAP may help shield an uncapped active site

A 5‑lipoxygenase-specific sequence motif impedes enzyme activity and confers dependence on a partner protein

© 2018 Elsevier B.V. Leukotrienes (LT) are lipid mediators of the inflammatory response that play key roles in diseases such as asthma and atherosclerosis. The precursor leukotriene A 4 (LTA 4 ) is synthesized from arachidonic acid (AA) by 5‑lipoxygenase (5-LOX), a membrane-associated enzyme, with the help of 5‑lipoxygenase-activating protein (FLAP), a nuclear transmembrane protein. In lipoxygenases the main chain carboxylate of the C-terminus is a ligand for the non-heme iron and thus part of the catalytic center. We investigated the role of a lysine-rich sequence (KKK 653–655 ) 20 amino acids upstream of the C-terminus unique to 5-LOX that might displace the main-chain carboxylate in the iron coordination sphere. A 5-LOX mutant in which KKK 653–655 is replaced by ENL was transfected into HEK293 cells in the absence and presence of FLAP. This mutant gave ~20-fold higher 5-LOX product levels in stimulated HEK cells relative to the wild-type 5-LOX. Co-expression of the enzymes with FLAP led to an equalization of 5-LOX products detected, with wild-type 5-LOX product levels increased and those from the mutant enzyme decreased. These data suggest that the KKK motif limits 5-LOX activity and that this attenuated activity must be compensated by the presence of FLAP as a partner protein for effective LT biosynthesis

The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP).

BACKGROUND AND PURPOSE: Leukotrienes (LTs) are inflammatory mediators produced via the 5-lipoxygenase (5-LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis. EXPERIMENTAL APPROACH: We analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell-free assays. The effectiveness of BRP-7 in vivo was evaluated in rat carrageenan-induced pleurisy and mouse zymosan-induced peritonitis. KEY RESULTS: BRP-7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5-LOX co-localization with FLAP. Neither the cellular viability nor the activity of 5-LOX in cell-free assays was affected by BRP-7, indicating that a functional FLAP is needed for BRP-7 to inhibit LTs, and FLAP bound to BRP-7 linked to a solid matrix. Compared with the FLAP inhibitor MK-886, BRP-7 did not significantly inhibit COX-1 or microsomal prostaglandin E2 synthase-1, implying the selectivity of BRP-7 for FLAP. Finally, BRP-7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels. CONCLUSIONS AND IMPLICATIONS: BRP-7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti-inflammatory effectiveness in vivo, with promising potential for further development