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Background Respiratory syncytial virus (RSV) infection is the primary cause of lower respiratory tract infections in children <5 years of age. Monocytes, especially in the respiratory tract, are suggested to contribute to RSV pathology, but their role is incompletely understood. With transcriptomic profiling of blood and airway monocytes, we describe the role of monocytes in severe RSV infection. Methods Tracheobronchial aspirates and blood samples were collected from control patients (n = 9) and those infected with RSV (n = 14) who were admitted to the pediatric intensive care unit. Monocytes (CD14+) were sorted and analyzed by RNA sequencing for transcriptomic profiling. Results Peripheral blood and airway monocytes of patients with RSV demonstrated increased expression of antiviral and interferon-responsive genes as compared with controls. Cytokine signaling showed a shared response between blood and airway monocytes while displaying responses that were more pronounced according to the tissue of origin. Airway monocytes upregulated additional genes related to migration and inflammation. Conclusions We found that the RSV-induced interferon response extends from the airways to the peripheral blood. Moreover, RSV induces a migration-promoting transcriptional program in monocytes. Unraveling the monocytic response and its role in the immune response to RSV infection could help the development of therapeutics to prevent severe disease. [ABSTRACT FROM AUTHOR]

A two-dimensional, continuous vortex sheet method for modeling and capturing the complexities of aircraft vortex flows is presented.

The Euler version of the NPARC code was used as a transonic flow simulator to determine the choking patterns of finite thickness airfoil subjected to transonic wind tunnel wall interference. Results show that transonic flow choking does not occur simultaneously at upper and lower surfaces and that wall interference can be used to solve angle of attack and Mach number problems. Results are incompatible with values derived from singular perturbation analysis

Blockage interference on propellers in a perforated-wall wind tunnel is studied using a one-component correction method. Static pressure tube measurements and the far field of the propeller in free air are used to determine the streamwise component of wall interference velocity at the wind tunnel boundaries. A sink term is used to model the radial contraction of the propulsive stream tube. Details of the evaluation method are discussed.

Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway critical for maintaining cellular homeostasis and viability, and is predominantly regarded as a rapid and dynamic cytoplasmic process. To increase our understanding of the transcriptional and epigenetic events associated with autophagy, we performed extensive genome-wide transcriptomic and epigenomic profiling after nutrient deprivation in human autophagy-proficient and autophagy-deficient cells. We observed that nutrient deprivation leads to the transcriptional induction of numerous autophagy-associated genes. These transcriptional changes are reflected at the epigenetic level (H3K4me3, H3K27ac, and H3K56ac) and are independent of autophagic flux. As a proof of principle that this resource can be used to identify novel autophagy regulators, we followed up on one identified target: EGR1 (early growth response 1), which indeed appears to be a central transcriptional regulator of autophagy by affecting autophagy-associated gene expression and autophagic flux. Taken together, these data stress the relevance of transcriptional and epigenetic regulation of autophagy and can be used as a resource to identify (novel) factors involved in autophagy regulation. [ABSTRACT FROM AUTHOR]

The article reports on the results of a feasibility study in 15 patients who had piezoelectric device for bone work in endoscopic anterior skull base surgery. Endoscopic transsphenoidal pituitary surgery has become the norm in the surgical treatment of most pituitary lesions. Despite excellentresults and postoperative CSF-leaks and skull base reconstructionsare still considerable issues.

Dilated cardiomyopathy (DCM) is a major cause of systolic heart failure and therefore a major public health issue. Our objective was to better understand the genetic bases of dilated cardiomyopathy. We conducted a 1000G based genome-wide association study for 9,152,885 SNPs on 2,719 sporadic DCM cases and 4,440 controls of European origin followed by a replication step. We then sought for the most likely culprit genes at the new replicated loci through a dedicated strategy including in silico data mining (including tissue specific gene expressions, expression and methylation quantitative trait loci) as well as functional 4C-sequencing analysis on iPSC-derived cardiomyocytes (Fig. 1). We identified two new DCM loci, on chromosome 3p25.1 (lead SNP rs62232870, p = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively) and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10−8 and 1.4 × 10−3, respectively), while confirming two previously identified ones, BAG3 and HSPB7. A Genetic Risk Score was built from the number of risk allele at these four loci and revealed a 27% increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). At chr3p25, our selection strategy pinpointed SLC6A6 as the most likely culprit gene. SLC6A6 encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, the same strategy strongly suggested SMARCB1 as the best candidate gene. This study provides new insights in the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure, with the potential for a therapeutic perspective especially through taurine modulation. [ABSTRACT FROM AUTHOR]

Radionecrosis (RN) in children treated for brain tumors represents a potentially severe long-term complication. Its diagnosis is challenging, since magnetic resonance imaging (MRI) cannot clearly discriminate between RN and tumor recurrence. A retrospective single-center study was undertaken to describe the incidence and clinical course of RN in a cohort of 107 children treated with external radiotherapy (RT) for various brain tumors between 1992 and 2012. During a median follow-up of 4.6 years (range 0.29-20.1 years), RN was implied by suspicious MRI findings in in 5 children (4.7 %), 5-131 months after RT. Suspicion was confirmed histologically (1 patient) or substantiated by FDG positron-emission tomography (FDG-PET, 2 patients) or by FDG-PET and MR spectroscopy (1 patient). Before developing RN, all 5 patients had received cytotoxic chemotherapy in addition to RT. In addition to standard treatment protocols, 2 patients had received further chemotherapy for progression or relapse. Median radiation dose expressed as the biologically equivalent total dose applied in 2 Gy fractions (EQD2) was 51.7 Gy (range 51.0-60.0 Gy). At RN onset, 4 children presented with neurological symptoms. Treatment of RN included resection (n = 1), corticosteroids (n = 2) and a combination of corticosteroids, hyperbaric oxygen (HBO) and bevacizumab (n = 1). One patient with asymptomatic RN was not treated. Complete radiological regression of the lesions was observed in all patients. Clinical symptoms normalized in 3 patients, whereas 2 developed permanent severe neurological deficits. RN represents a severe long-term treatment complication in children with brain tumors. The spectrum of clinical presentation is wide; ranging from asymptomatic lesions to progressive neurological deterioration. FDG-PET and MR spectroscopy may be useful for distinguishing between RN and tumor recurrence. Treatment options in patients with symptomatic RN include conservative management (steroids, HBO, bevacizumab) and surgical resection. [ABSTRACT FROM AUTHOR]

Transcriptional activity of Forkhead box transcription factor class O (FOXO) proteins can result in a variety of cellular outcomes depending on cell type and activating stimulus. These transcription factors are negatively regulated by the phosphoinositol 3-kinase (PI3K)-protein kinase B (PKB) signaling pathway, which is thought to have a pivotal role in regulating survival of tumor cells in a variety of cancers. Recently, it has become clear that FOXO proteins can promote resistance to anti-cancer therapeutics, designed to inhibit PI3K-PKB activity, by inducing the expression of proteins that provide feedback at different levels of this pathway. We questioned whether such a feedback mechanism may also exist directly at the level of FOXO-induced transcription. To identify critical modulators of FOXO transcriptional output, we performed gene expression analyses after conditional activation of key components of the PI3K-PKB-FOXO signaling pathway and identified FOXP1 as a direct FOXO transcriptional target. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that FOXP1 binds enhancers that are pre-occupied by FOXO3. By sequencing the transcriptomes of cells in which FOXO is specifically activated in the absence of FOXP1, we demonstrate that FOXP1 can modulate the expression of a specific subset of FOXO target genes, including inhibiting expression of the pro-apoptotic gene BIK. FOXO activation in FOXP1-knockdown cells resulted in increased cell death, demonstrating that FOXP1 prevents FOXO-induced apoptosis. We therefore propose that FOXP1 represents an important modulator of FOXO-induced transcription, promoting cellular survival. [ABSTRACT FROM AUTHOR]

Focuses on the vortex merger factor in the aircraft wake turbulence. Wing load distribution; Interaction of a vortex with an equally oriented shear layer.

Describes an application of the inviscid (Euler) version of the NPARC code to a finite thickness airfoil inside a test section with impermeable walls. Boundary conditions; Choking interval; Freestream conditions.

Deals with a study which examined the effect of an aircraft's vortex wake on the flight of a following aircraft. in the presence of a crosswind shear. Background on wake turbulence; Numerical simulation; Conclusions.

Hypothermic machine perfusion (HMP) is an emerging method of donor organ preservation. Its application for heart transplantation is currently being studied in a clinical trial. Due to the limited ability to assess graft quality during HMP, a reliable prognostic biomarker is needed for quality assessment and prediction of heart function after implantation. This study was designed to identify prognostic biomarkers during HMP of porcine hearts using a multitargeted approach. A total of 7 slaughterhouse porcine hearts were subjected to 4 hours HMP, followed by 4 hours of normothermic machine perfusion (NMP) for functional assessment. Perfusate samples were collected at baseline and after 4 hours of HMP, for analysis of damage markers and cell-free DNA. Additionally, an Olink Organ Damage T96 panel was performed, after which proteins of interest were identified based on a significant change in expression between baseline and 4 hours HMP. Prognostic value of each protein of interest was determined by correlating expression values at the end of HMP with cardiac function after 4 hours of NMP using Spearman's R. Both ammonia (r=0.8571; P=0.0238) and troponin-I (r=0.7857; P=0.0480) were positively correlated with cardiac index, while lactate (r=-0.8108; P=0.0381) was negatively correlated with coronary flow index. Both mitochondrial and nuclear cell-free DNA displayed a decrease in expression during HMP and showed no significant correlation with cardiac function. Olink data revealed that YES1 was negatively correlated with cardiac index (r=-0.8571; P=0.0238), coronary flow (r=-0.7857; P=0.0480) and coronary flow index (r=-0.8571; P=0.0238). Our study identifies YES1 as a potential prognostic biomarker when assessed during HMP, as reflected by the negative correlation with cardiac function. Future research into the translational value of YES1 and the involved physiological pathways is needed. Furthermore, troponin-I expression during HMP shows an interesting inverse correlation with functional outcome. We hypothesize that the increased troponin-I values during HMP are reflective of improved wash-out of damage markers due to better preserved microvasculature. This might explain the improved function of hearts with high troponin-I expression during HMP. [ABSTRACT FROM AUTHOR]