Vertical Governance between Airlines and Airports - A Transaction Cost Analysis

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.With airport privatization and infrastructure expansion projects taking place in the liberalized European air transport market, airport and airline companies are critically reevaluating their vertical governance structures. This paper analyzes the comparative efficiency of vertical governance structures in the airport-airline supply relationship. Using transaction cost economics as the lens of analysis, we develop propositions and present supporting qualitative case studies. Our propositions state that hub airlines and hub airports seek specialized governance structures, while value-based carriers and base airports enter into long-term contracts supported by complementary safeguards. These privately crafted governance modes complement or even replace external regulation

Phenotypic plasticity of male calls in two populations of the katydid Neoconocephalus triops (Insecta: Tettigoniidae)

The ability to respond to environmental changes plays a crucial role for coping with environmental stressors related to climate change. Substantial changes in environmental conditions can overcome developmental homeostasis, exposing cryptic genetic variation. The katydid Neoconocephalus triops is a tropical species that extended its range to the more seasonal environment of North America where it has two reproductive generations per year. The harsher winter conditions required adults to diapause which resulted in substantially different mating calls of the diapausing winter animals compared to the non-overwintering summer animals in northern Florida. The summer call corresponds to that of tropical populations, whereas the winter call represents the alternative call phenotype. We quantified call plasticity in a tropical (Puerto Rico) and a temperate population of N. triops (Florida) that differ in experiencing winter conditions in their geographic regions. We hypothesized that the plastic call traits, i.e., double-pulse rate and call structure, are regulated independently. Further, we hypothesized that phenotypic plasticity of double-pulse rate results in quantitative changes, whereas that of call structure in qualitative changes. We varied the photoperiod and duration of diapause during male juvenile and adult development during rearing and analyzed the double-pulse rate and call structure of the animals. Double-pulse rate changed in a quantitative fashion in both populations and significant changes appeared at different developmental points, i.e., the double-pulse rate slowed down during juvenile development in Florida, whereas during adult diapause in Puerto Rico. In the Florida population, both the number of males producing and the proportion of total call time covered by the alternative call structure (= continuous calls) increased with duration spent in diapause. In the Puerto Rico population, expression of the alternative call structure was extremely rare. Our results suggest that the expression of both pulse rate and call structure was quantitative and not categorical. Our systematic variation of environmental variables demonstrated a wide range of phenotypic variation that can be induced during development. Our study highlights the evolutionary potential of hidden genetic variation and phenotypic plasticity when confronted with rapidly changing environments and their potential role in providing variation necessary for communication systems to evolve

Compartmentalised expression of Delta-like 1 in epithelial somites is required for the formation of intervertebral joints

<p>Abstract</p> <p>Background</p> <p>Expression of the mouse <it>Delta-like 1 </it>(<it>Dll1</it>) gene in the presomitic mesoderm and in the caudal halves of somites of the developing embryo is required for the formation of epithelial somites and for the maintenance of caudal somite identity, respectively. The rostro-caudal polarity of somites is initiated early on within the presomitic mesoderm in nascent somites. Here we have investigated the requirement of restricted <it>Dll1 </it>expression in caudal somite compartments for the maintenance of rostro-caudal somite polarity and the morphogenesis of the axial skeleton. We did this by overexpressing a functional copy of the <it>Dll1 </it>gene throughout the paraxial mesoderm, in particular in anterior somite compartments, during somitogenesis in transgenic mice.</p> <p>Results</p> <p>Epithelial somites were generated normally and appeared histologically normal in embryos of two independent <it>Dll1 </it>over-expressing transgenic lines. Gene expression analyses of rostro-caudal marker genes suggested that over-expression of <it>Dll1 </it>without restriction to caudal compartments was not sufficient to confer caudal identity to rostral somite halves in transgenic embryos. Nevertheless, <it>Dll1 </it>over-expression caused dysmorphologies of the axial skeleton, in particular, in morphological structures that derive from the articular joint forming compartment of vertebrae. Accordingly, transgenic animals exhibited missing or reduced intervertebral discs, rostral and caudal articular processes as well as costal heads of ribs. In addition, the midline of the vertebral column did not develop normally. Transgenic mice had open neural arches and split vertebral bodies with ectopic pseudo-growth plates. Endochondral bone formation and ossification in the developing vertebrae were delayed.</p> <p>Conclusion</p> <p>The mice overexpressing <it>Dll1 </it>exhibit skeletal dysmorphologies that are also evident in several mutant mice with defects in somite compartmentalisation. The <it>Dll1 </it>transgenic mice demonstrate that vertebral dysmorphologies such as bony fusions of vertebrae and midline vertebral defects can occur without apparent changes in somitic rostro-caudal marker gene expression. Also, we demonstrate that the over-expression of the <it>Dll1 </it>gene in rostral epithelial somites is not sufficient to confer caudal identity to rostral compartments. Our data suggest that the restricted <it>Dll1 </it>expression in caudal epithelial somites may be particularly required for the proper development of the intervertebral joint forming compartment.</p

Minimal instructions improve the performance of laypersons in the use of semiautomatic and automatic external defibrillators

INTRODUCTION: There is evidence that use of automated external defibrillators (AEDs) by laypersons improves rates of survival from cardiac arrest, but there is no consensus on the optimal content and duration of training for this purpose. In this study we examined the use of semiautomatic or automatic AEDs by laypersons who had received no training (intuitive use) and the effects of minimal general theoretical instructions on their performance. METHODS: In a mock cardiac arrest scenario, 236 first year medical students who had not previously attended any preclinical courses were evaluated in their first study week, before and after receiving prespecified instructions (15 min) once. The primary end-point was the time to first shock for each time point; secondary end-points were correct electrode pad positioning, safety of the procedure and the subjective feelings of the students. RESULTS: The mean time to shock for both AED types was 81.2 ± 19.2 s (range 45–178 s). Correct pad placement was observed in 85.6% and adequate safety in 94.1%. The time to shock after instruction decreased significantly to 56.8 ± 9.9 s (range 35–95 s; P ≤ 0.01), with correct electrode placement in 92.8% and adequate safety in 97%. The students were significantly quicker at both evaluations using the semiautomatic device than with the automatic AED (first evaluation: 77.5 ± 20.5 s versus 85.2 ± 17 s, P ≤ 0.01; second evaluation: 55 ± 10.3 s versus 59.6 ± 9.6 s, P ≤ 0.01). CONCLUSION: Untrained laypersons can use semiautomatic and automatic AEDs sufficiently quickly and without instruction. After one use and minimal instructions, improvements in practical performance were significant. All tested laypersons were able to deliver the first shock in under 1 min

miR-34a is upregulated inAIP-mutated somatotropinomas and promotes octreotide resistance

Pituitary adenomas (PAs) are intracranial tumors associated with significant morbidity due to hormonal dysregulation, mass effects and have a heavy treatment burden. Growth hormone (GH)-secreting PAs (somatotropinomas) cause acromegaly-gigantism. Genetic forms of somatotropinomas due to germlineAIPmutations (AIPmut+) have an early onset and are aggressive and resistant to treatment with somatostatin analogs (SSAs), including octreotide. The molecular underpinnings of these clinical features remain unclear. We investigated the role of miRNA dysregulation inAIPmut+ vsAIPmut- PA samples by array analysis. miR-34a and miR-145 were highly expressed inAIPmut+ vsAIPmut- somatotropinomas. Ectopic expression ofAIPmut (p.R271W) inAip(-/-)mouse embryonic fibroblasts (MEFs) upregulated miR-34a and miR-145, establishing a causal link betweenAIPmut and miRNA expression. In PA cells (GH3), miR-34a overexpression promoted proliferation, clonogenicity, migration and suppressed apoptosis, whereas miR-145 moderately affected proliferation and apoptosis. Moreover, high miR-34a expression increased intracellular cAMP, a critical mitogenic factor in PAs. Crucially, high miR-34a expression significantly blunted octreotide-mediated GH inhibition and antiproliferative effects. miR-34a directly targetsGnai2encoding G alpha i2, a G protein subunit inhibiting cAMP production. Accordingly, G alpha i2 levels were significantly lower inAIPmut+ vsAIPmut- PA. Taken together, somatotropinomas withAIPmutations overexpress miR-34a, which in turn downregulates G alpha i2 expression, increases cAMP concentration and ultimately promotes cell growth. Upregulation of miR-34a also impairs the hormonal and antiproliferative response of PA cells to octreotide. Thus, miR-34a is a novel downstream target of mutantAIPthat promotes a cellular phenotype mirroring the aggressive clinical features ofAIPmut+ acromegaly.Peer reviewe

BET bromodomain protein inhibition is a therapeutic option for medulloblastoma

Medulloblastoma is the most common malignant brain tumor of childhood, and represents a significant clinical challenge in pediatric oncology, since overall survival currently remains under 70%. Patients with tumors overexpressing MYC or harboring a MYC oncogene amplification have an extremely poor prognosis. Pharmacologically inhibiting MYC expression may, thus, have clinical utility given its pathogenetic role in medulloblastoma. Recent studies using the selective small molecule BET inhibitor, JQ1, have identified BET bromodomain proteins, especially BRD4, as epigenetic regulatory factors for MYC and its targets. Targeting MYC expression by BET inhibition resulted in antitumoral effects in various cancers. Our aim here was to evaluate the efficacy of JQ1 against preclinical models for high-risk MYC-driven medulloblastoma. Treatment of medulloblastoma cell lines with JQ1 significantly reduced cell proliferation and preferentially induced apoptosis in cells expressing high levels of MYC. JQ1 treatment of medulloblastoma cell lines downregulated MYC expression and resulted in a transcriptional deregulation of MYC targets, and also significantly altered expression of genes involved in cell cycle progression and p53 signalling. JQ1 treatment prolonged the survival of mice harboring medulloblastoma xenografts and reduced the tumor burden in these mice. Our preclinical data provide evidence to pursue testing BET inhibitors, such as JQ1, as molecular targeted therapeutic options for patients with high-risk medulloblastomas overexpressing MYC or harboring MYC amplifications

Targeting tachykinin receptors in neuroblastoma

Neuroblastoma is the most common extracranial tumor in children. Despite aggressive multimodal treatment, high-risk neuroblastoma remains a clinical challenge with survival rates below 50%. Adding targeted drugs to first-line therapy regimens is a promising approach to improve survival in these patients. TACR1 activation by substance P has been reported to be mitogenic in cancer cell lines. Tachykinin receptor (TACR1) antagonists are approved for clinical use as an antiemetic remedy since 2003. Tachykinin receptor inhibition has recently been shown to effectively reduce growth of several tumor types. Here, we report that neuroblastoma cell lines express TACR1, and that targeting TACR1 activity significantly reduced cell viability and induced apoptosis in neuroblastoma cell lines. Gene expression profiling revealed that TACR1 inhibition repressed E2F2 and induced TP53 signaling. Treating mice harboring established neuroblastoma xenograft tumors with Aprepitant also significantly reduced tumor burden. Thus, we provide evidence that the targeted inhibition of tachykinin receptor signaling shows therapeutic efficacy in preclinical models for high-risk neuroblastoma

A method for measuring the amount of hoar frost formation in the recuperation channels of ventilation systems using the adjustable mathematical model of this process

The paper presents a method for measuring the amount of hoar frost formation in the recuperation channels of ventilation systems using the adjustable mathematical model of the hoar frost process. The principle is based on the fact that the contour of the adjustment of the hoar frost model is included in the measurement in accordance with the measured pressure drop, which is proportional to the amount of hoar frost. Unlike the known measurement methods, it is proposed to use the state variables of the mathematical model as the measured value. These state variables are not subject to non-deterministic interferences and random influences. The paper presents simulation results confirming the adequacy of the dynamic model. In conclusion, an example of the use of a recuperation channel in the defrost management system is given

Pathway focused protein profiling indicates differential function for IL-1B, -18 and VEGF during initiation and resolution of lung inflammation evoked by carbon nanoparticle exposure in mice

<p>Abstract</p> <p>Background</p> <p>Carbonaceous nanoparticles possess an emerging source of human exposure due to the massive release of combustion products and the ongoing revolution in nanotechnology. Pulmonary inflammation caused by deposited nanoparticles is central for their adverse health effects. Epidemiological studies suggest that individuals with favourable lung physiology are at lower risk for particulate matter associated respiratory diseases probably due to efficient control of inflammation and repair process. Therefore we selected a mouse strain C3H/HeJ (C3) with robust lung physiology and exposed it to moderately toxic carbon nanoparticles (CNP) to study the elicited pulmonary inflammation and its resolution.</p> <p>Methods</p> <p>5 μg, 20 μg and 50 μg CNP were intratracheally (i.t.) instilled in C3 mice to identify the optimal dose for subsequent time course studies. Pulmonary inflammation was assessed using histology, bronchoalveolar lavage (BAL) analysis and by a panel of 62 protein markers.</p> <p>Results</p> <p>1 day after instillation of CNP, C3 mice exhibited a typical dose response, with the lowest dose (5 μg) representing the 'no effect level' as reflected by polymorphonuclear leucocyte (PMN), and BAL/lung concentrations of pro-inflammatory proteins. Histological analysis and BAL-protein concentration did not reveal any evidence of tissue injury in 20 μg CNP instilled animals. Accordingly time course assessment of the inflammatory response was performed after 3 and 7 days with this dose (20 μg). Compared to day 1, BAL PMN counts were significantly decreased at day 3 and completely returned to normal by day 7. We have identified protein markers related to the acute response and also to the time dependent response in lung and BAL. After complete resolution of PMN influx on day 7, we detected elevated concentrations of 20 markers that included IL1B, IL18, FGF2, EDN1, and VEGF in lung and/or BAL. Biological pathway analysis revealed these factors to be involved in a closely regulated molecular cascade with IL1B/IL18 as upstream and FGF2/EDN1/VEGF as downstream molecules.</p> <p>Conclusion</p> <p>Considering the role of VEGF, FGF2 and EDN1 in lung development and morphogenesis together with the lack of any evident tissue damage we suggest a protective/homeostatic machinery to be associated in lungs of stable organisms to counter the CNP challenge as a precautionary measure.</p

Acetabular Peri-Prosthetic Fractures-A Narrative Review.

Acetabular peri-prosthetic fractures are rare but their incidence is rising due to the increased prevalence of total hip arthroplasty, the increasing life expectancy and the growing functional demand of an ageing population, the incidence of primary total hip arthroplasty is increasing. They are either intra-operative or post-operative and have various aetiologies. Several factors such as implant stability, bone loss, remaining bone stock, fracture pattern, timing, age and co-morbidities of the patients must be considered for adequate treatment. To date, the literature on this subject has been sparse and no universally recognized treatment algorithm exists. Their rarity makes them a little-known entity and their surgical management represents a challenge for most orthopaedic surgeons. This review aims to present an update on epidemiology, the diagnostic work up, existing classification systems, surgical approaches and therapeutic options for acetabular peri-prosthetic fractures