259 research outputs found

    Vertical Governance between Airlines and Airports - A Transaction Cost Analysis

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    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

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

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    <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

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    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

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    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

    Targeting tachykinin receptors in neuroblastoma

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    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

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    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

    Acetabular Peri-Prosthetic Fractures-A Narrative Review.

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    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

    Impaired resolution of inflammatory response in the lungs of JF1/Msf mice following carbon nanoparticle instillation

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    <p>Abstract</p> <p>Background</p> <p>Declined lung function is a risk factor for particulate matter associated respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). Carbon nanoparticles (CNP) are a prominent component of outdoor air pollution that causes pulmonary toxicity mainly through inflammation. Recently we demonstrated that mice (C3H/HeJ) with higher than normal pulmonary function resolved the elicited pulmonary inflammation following CNP exposure through activation of defense and homeostasis maintenance pathways. To test whether CNP-induced inflammation is affected by declined lung function, we exposed JF1/Msf (JF1) mice with lower than normal pulmonary function to CNP and studied the pulmonary inflammation and its resolution.</p> <p>Methods</p> <p>5 μg, 20 μg and 50 μg CNP (Printex 90) were intratracheally instilled in JF1 mice to determine the dose response and the time course of inflammation over 7 days (20 μg dosage). Inflammation was assessed using histology, bronchoalveolar lavage (BAL) analysis and by a panel of 62 protein markers.</p> <p>Results</p> <p>24 h after instillation, 20 μg and 50 μg CNP caused a 25 fold and 19 fold increased polymorphonuclear leucocytes (PMN) respectively while the 5 μg represented the 'no observable adverse effect level' as reflected by PMN influx (9.7 × 10E3 vs 8.9 × 10E3), and BAL/lung concentrations of pro-inflammatory cytokines. Time course assessment of the inflammatory response revealed that compared to day1 the elevated BAL PMN counts (246.4 × 10E3) were significantly decreased at day 3 (72.9 × 10E3) and day 7 (48.5 × 10E3) but did not reach baseline levels indicating slow PMN resolution kinetics. Strikingly on day 7 the number of macrophages doubled (455.0 × 10E3 vs 204.7 × 10E3) and lymphocytes were 7-fold induced (80.6 × 10E3 vs 11.2 × 10E3) compared to day1. At day 7 elevated levels of IL1B, TNF, IL4, MDC/CCL22, FVII, and vWF were detected in JF1 lungs which can be associated to macrophage and lymphocyte activation.</p> <p>Conclusion</p> <p>This explorative study indicates that JF1 mice with impaired pulmonary function also exhibits delayed resolution of particle mediated lung inflammation as evident from elevated PMN and accumulation of macrophages and lymphocytes on day7. It is plausible that elevated levels of IL1B, IL4, TNF, CCL22/MDC, FVII and vWF counteract defense and homeostatic pathways thereby driving this phenomenon.</p

    Maternal Pre-Pregnancy Obesity Is Associated with Altered Placental Transcriptome

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    <p><b>(A)</b> Principal component analysis (PCA) of term placental gene expression profiles in obese (Ob_ N°) and normal weight women (N_N°). <b>(B)</b> Cluster analysis of dysregulated genes in term placentas from obese (Ob_ N°) <i>vs</i>. normal weight women (N_N°). Red represents genes with high expression levels and green represents genes with low expression levels.</p
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