Multicarrier Approaches for High-Baudrate Optical-Fiber Transmission Systems with a Single Coherent Receiver

In this paper, we show the remarkable timing error (TE) and residual chromatic dispersion (CD) tolerance improvements of the filter bank multicarrier (FBMC) over orthogonal frequency division multiplexing (OFDM) for high-baudrate spectral slicing transmitter and single coherent receiver transmissions. For a 512 Gb/s 16 quadrature amplitude modulated (16QAM) spectrum slicing system at 1600 km of fiber transmission, the FBMC-based system reduces TE and residual CD penalties by more than 1.5 dB and 3 dB, in comparison to the OFDM-based system, respectively

Lack of interest in physical activity : individual and environmental attributes in adults across Europe : the SPOTLIGHT project

A considerable proportion of European adults report little or no interest in physical activity. Identifying individual-level and environmental-level characteristics of these individuals can help designing effective interventions and policies to promote physical activity. This cross-sectional study additionally explored associations between level of interest and physical activity, after controlling for other individual and environmental variables. Measures of objective and perceived features of the physical environment of residence, self-reported physical activity and other lifestyle behaviors, barriers towards physical activity, general health, and demographics were obtained from 5205 European adults participating in the 2014 online SPOTLIGHT survey. t-Tests, chi-square tests, and generalized estimating equations with negative binomial log-link function were conducted. Adults not interested in physical activity reported a higher BMI and a lower self-rated health, were less educated, and to a smaller extent female and less frequently employed. They were more prone to have less healthy eating habits, and to perceive more barriers towards physical activity. Only minor differences were observed in environmental attributes: the non-interested were slightly more likely to live in neighborhoods objectively characterized as less aesthetic and containing more destinations, and perceived as less functional, safe, and aesthetic. Even after controlling for other individual and environmental factors, interest in physical activity remained a significant correlate of physical activity, supporting the importance of this association. This study is among the first to describe characteristics of individuals with reduced interest in physical activity, suggesting that (lack of) interest is a robust correlate of physical activity in several personal and environmental conditions

Glucocorticoid receptor DNA methylation and childhood trauma in chronic fatigue syndrome patients

Although the precise mechanisms are not yet understood, previous studies have suggested that chronic fatigue syndrome (CFS) is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and trauma in early childhood. Consistent with findings suggesting that early life stress-induced DNA methylation changes may underlie dysregulation of the HPA axis, we previously found evidence for the involvement of glucocorticoid receptor (GR) gene (NR3C1) methylation in whole blood of CFS patients. Methods In the current study, we assessed NR3C1-1F region DNA methylation status in peripheral blood from a new and independent sample of 80 female CFS patients and 91 female controls. In CFS patients, history of childhood trauma subtypes was evaluated using the Childhood Trauma Questionnaire short form (CTQ-SF). Results Although absolute methylation differences were small, the present study confirms our previous findings of NR3C1-1F DNA hypomethylation at several CpG sites in CFS patients as compared to controls. Following multiple testing correction, only CpG_8 remained significant (DNA methylation difference: 1.3% versus 1.5%, p < 0.001). In addition, we found associations between DNA methylation and severity of fatigue as well as with childhood emotional abuse in CFS patients, although these findings were not significant after correction for multiple testing. Conclusions In conclusion, we replicated findings of NR3C1-1F DNA hypomethylation in CFS patients versus controls. Our results support the hypothesis of HPA axis dysregulation and enhanced GR sensitivity in CFS

Conditional deletion of epithelial IKKβ impairs alveolar formation through apoptosis and decreased VEGF expression during early mouse lung morphogenesis

<p>Abstract</p> <p>Background</p> <p>Alveolar septation marks the beginning of the transition from the saccular to alveolar stage of lung development. Inflammation can disrupt this process and permanently impair alveolar formation resulting in alveolar hypoplasia as seen in bronchopulmonary dysplasia in preterm newborns. NF-κB is a transcription factor central to multiple inflammatory and developmental pathways including dorsal-ventral patterning in fruit flies; limb, mammary and submandibular gland development in mice; and branching morphogenesis in chick lungs. We have previously shown that epithelial overexpression of NF-κB accelerates lung maturity using transgenic mice. The purpose of this study was to test our hypothesis that targeted deletion of NF-κB signaling in lung epithelium would impair alveolar formation.</p> <p>Methods</p> <p>We generated double transgenic mice with lung epithelium-specific deletion of IKKβ, a known activating kinase upstream of NF-κB, using a cre-<it>loxP </it>transgenic recombination strategy. Lungs of resulting progeny were analyzed at embryonic and early postnatal stages to determine specific effects on lung histology, and mRNA and protein expression of relevant lung morphoreulatory genes. Lastly, results measuring expression of the angiogenic factor, VEGF, were confirmed <it>in vitro </it>using a siRNA-knockdown strategy in cultured mouse lung epithelial cells.</p> <p>Results</p> <p>Our results showed that IKKβ deletion in the lung epithelium transiently decreased alveolar type I and type II cells and myofibroblasts and delayed alveolar formation. These effects were mediated through increased alveolar type II cell apoptosis and decreased epithelial VEGF expression.</p> <p>Conclusions</p> <p>These results suggest that epithelial NF-κB plays a critical role in early alveolar development possibly through regulation of VEGF.</p

Potential human transmission of amyloid β pathology: surveillance and risks

Studies in experimental animals show transmissibility of amyloidogenic proteins associated with prion diseases, Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Although these data raise potential concerns for public health, convincing evidence for human iatrogenic transmission only exists for prions and amyloid β after systemic injections of contaminated growth hormone extracts or dura mater grafts derived from cadavers. Even though these procedures are now obsolete, some reports raise the possibility of iatrogenic transmission of amyloid β through putatively contaminated neurosurgical equipment. Iatrogenic transmission of amyloid β might lead to amyloid deposition in the brain parenchyma and blood vessel walls, potentially resulting in cerebral amyloid angiopathy after several decades. Cerebral amyloid angiopathy can cause life-threatening brain haemorrhages; yet, there is no proof that the transmission of amyloid β can also lead to Alzheimer's dementia. Large, long-term epidemiological studies and sensitive, cost-efficient tools to detect amyloid are needed to better understand any potential routes of amyloid β transmission and to clarify whether other similar proteopathic seeds, such as tau or α-synuclein, can also be transferred iatrogenically

Maternal hypoxia decreases capillary supply and increases metabolic inefficiency leading to divergence in myocardial oxygen supply and demand

Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO2=0.12) at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. 14 C-labelled glucose and 3 H-palmitate were provided as substrates and metabolism quantified from recovery of 14CO2 and 3 H2O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05), despite recording a 2-fold increase in glucose oxidation (P<0.01) and 2.5-fold increase (P<0.01) in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01) and suppressed palmitate oxidation (P<0.05), suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01), although pyruvate dehydrogenase sensitivity to insulin was lost (NS), while citrate synthase activity declined by 30% (P<0.001) and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001). Calculated metabolic efficiency decreased 4-fold (P<0.01) for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to preserve local PO2, minimising regions of hypoxia and hence maximising the area of myocardium able to preserve cardiac output following maternal hypoxia

Vascular Endothelial Growth Factor (VEGF) isoform expression and activity in human and murine lung injury

<p>Abstract</p> <p>Background</p> <p>The properties of vascular endothelial growth factor (VEGF) as a potent vascular permogen and mitogen have led to investigation of its potential role in lung injury. Alternate spliced VEGF transcript generates several isoforms with potentially differing functions. The purpose of this study was to determine VEGF isoform expression and source in normal and ARDS subjects and investigate the expression and regulation of VEGF isoforms by human alveolar type 2 (ATII) cells.</p> <p>Methods</p> <p>VEGF protein expression was assessed immunohistochemically in archival normal and ARDS human lung tissue. VEGF isoform mRNA expression was assessed in human and murine lung tissue. Purified ATII cells were cultured with proinflammatory cytokines prior to RNA extraction/cell supernatant sampling/proliferation assay.</p> <p>Measurements and Main Results</p> <p>VEGF was expressed on alveolar epithelium, vascular endothelium and alveolar macrophages in normal and ARDS human lung tissue. Increases in VEGF expression were detected in later ARDS in comparison to both normal subjects and early ARDS (p < 0.001). VEGF₁₂₁, VEGF₁₆₅and VEGF₁₈₉isoform mRNA expression increased in later ARDS (p < 0.05). The ratio of soluble to cell-associated isoforms was lower in early ARDS than normal subjects and later ARDS and also in murine lung injury. ATII cells constitutionally produced VEGF₁₆₅and VEGF₁₂₁protein which was increased by LPS (p < 0.05). VEGF₁₆₅upregulated ATII cell proliferation (p < 0.001) that was inhibited by soluble VEGF receptor 1 (<it>sflt</it>) (p < 0.05).</p> <p>Conclusion</p> <p>These data demonstrate that changes in VEGF isoform expression occur in ARDS which may be related to their production by and mitogenic effect on ATII cells; with potentially significant clinical consequences.</p

Angiogenesis gene expression in murine endothelial cells during post-pneumonectomy lung growth

Although blood vessel growth occurs readily in the systemic bronchial circulation, angiogenesis in the pulmonary circulation is rare. Compensatory lung growth after pneumonectomy is an experimental model with presumed alveolar capillary angiogenesis. To investigate the genes participating in murine neoalveolarization, we studied the expression of angiogenesis genes in lung endothelial cells. After left pneumonectomy, the remaining right lung was examined on days 3, 6, 14 and 21days after surgery and compared to both no surgery and sham thoracotomy controls. The lungs were enzymatically digested and CD31+ endothelial cells were isolated using flow cytometry cell sorting. The transcriptional profile of the CD31+ endothelial cells was assessed using quantitative real-time polymerase chain reaction (PCR) arrays. Focusing on 84 angiogenesis-associated genes, we identified 22 genes with greater than 4-fold regulation and significantly enhanced transcription (p <.05) within 21 days of pneumonectomy. Cluster analysis of the 22 genes indicated that changes in gene expression did not occur in a single phase, but in at least four waves of gene expression: a wave demonstrating decreased gene expression more than 3 days after pneumonectomy and 3 sequential waves of increased expression on days 6, 14, and 21 after pneumonectomy. These findings indicate that a network of gene interactions contributes to angiogenesis during compensatory lung growth