Self-similar propagation of parabolic pulses in normal-dispersion fiber amplifiers

Pulse propagation in high-gain optical fiber amplifiers with normal group-velocity dispersion has been studied by self-similarity analysis of the nonlinear Schrödinger equation with gain. For an amplifier with a constant distributed gain, an exact asymptotic solution has been found that corresponds to a linearly chirped parabolic pulse that propagates self-similarly in the amplifier, subject to simple scaling rules. The evolution of an arbitrary input pulse to an asymptotic solution is associated with the development of low-amplitude wings on the parabolic pulse whose functional form has also been found by means of self-similarity analysis. These theoretical results have been confirmed with numerical simulations. A series of guidelines for the practical design of fiber amplifiers to operate in the asymptotic parabolic pulse regime has also been developed

Feeding cancer's sweet tooth: Specialized tumour vasculature shuttles glucose in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal neoplasm characterized by a 'fortress' of thick collagen fibres, abundant myofibroblasts, and paradoxically reduced vascularization compared to normal pancreas. Despite these features, PDAC shows no reduction in the uptake of glucose that fuels tumour cell survival. In new work published in The Journal of Pathology, Saiyin and colleagues have identified a novel adaptation of PDAC tumour endothelium; namely, 'hairy-like' basal microvilli that increase the total vascular surface area and correlate with regions of highest glucose uptake. Since basal microvilli are not present on normal pancreatic blood vessels, their presence may add diagnostic value and blocking their function is a potential new treatment strategy for PDAC. This novel finding of basal microvilli on PDAC endothelium is a striking example of how phenotypic plasticity in tumour blood vessels contributes to tumour growth and progression, independent of conventional modes of angiogenesis

A systematic review of evidence for the psychometric properties of the Strengths and Difficulties Questionnaire

This paper synthesised evidence for the validity and reliability of the Strengths and Difficulties Questionnaire in children aged 3-5. A systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines was carried out. Study quality was rated using the Consensus-based Standards for the Selection of Health Measurement Instruments. 41 studies were included (56 manuscripts). Two studies examined content and cultural validity, revealing issues with some questions. Six studies discussed language validations with changes to some wording recommended. There was good evidence for discriminative validity (Area Under the Curve ≥0.80), convergent validity (weighted average correlation coefficients ≥0.50, except for the Prosocial scale), and the 5-factor structural validity. There was limited support for discriminant validity. Sensitivity was below 70% and specificity above 70% in most studies that examined this. Internal consistency of the total difficulty scale was good (weighted average Cronbach’s alpha parents’ and teachers’ version 0.79 and 0.82) but weaker for other subscales (weighted average parents’ and teachers’ range 0.49-0.69 and 0.69-0.83). Inter-rater reliability between parents was moderate (correlation coefficients range 0.42-0.64) and between teachers strong (range 0.59-0.81). Cross-informant consistency was weak to moderate (weighted average correlation coefficients range 0.25-0.45). Test-retest reliability was mostly inadequate. In conclusion, the lack of evidence for cultural validity, criterion validity and test-retest reliability should be addressed given wide-spread implementation of the tool in routine clinical practice. The moderate level of consistency between different informants indicate that an assessment of a pre-schooler should not rely on a single informant

Endothelial miR-30c suppresses tumor growth via inhibition of TGF-β–induced Serpine1

In tumors, extravascular fibrin forms provisional scaffolds for endothelial cell (EC) growth and motility during angiogenesis. We report that fibrin-mediated angiogenesis was inhibited and tumor growth delayed following postnatal deletion of Tgfbr2 in the endothelium of Cdh5-CreERT2 Tgfbr2fl/fl mice (Tgfbr2iECKOmice). ECs from Tgfbr2iECKO mice failed to upregulate the fibrinolysis inhibitor plasminogen activator inhibitor 1 (Serpine1, also known as PAI-1), due in part to uncoupled TGF-β–mediated suppression of miR-30c. Bypassing TGF-β signaling with vascular tropic nanoparticles that deliver miR-30c antagomiRs promoted PAI-1–dependent tumor growth and increased fibrin abundance, whereas miR-30c mimics inhibited tumor growth and promoted vascular-directed fibrinolysis in vivo. Using single-cell RNA-Seq and a NanoString miRNA array, we also found that subtypes of ECs in tumors showed spectrums of Serpine1 and miR-30c expression levels, suggesting functional diversity in ECs at the level of individual cells; indeed, fresh EC isolates from lung and mammary tumor models had differential abilities to degrade fibrin and launch new vessel sprouts, a finding that was linked to their inverse expression patterns of miR-30c and Serpine1 (i.e., miR-30chi Serpine1lo ECs were poorly angiogenic and miR-30clo Serpine1hi ECs were highly angiogenic). Thus, by balancing Serpine1 expression in ECs downstream of TGF-β, miR-30c functions as a tumor suppressor in the tumor microenvironment through its ability to promote fibrin degradation and inhibit blood vessel formation

Dispersion and collapse in stochastic velocity fields on a cylinder

The dynamics of fluid particles on cylindrical manifolds is investigated. The velocity field is obtained by generalizing the isotropic Kraichnan ensemble, and is therefore Gaussian and decorrelated in time. The degree of compressibility is such that when the radius of the cylinder tends to infinity the fluid particles separate in an explosive way. Nevertheless, when the radius is finite the transition probability of the two-particle separation converges to an invariant measure. This behavior is due to the large-scale compressibility generated by the compactification of one dimension of the space

Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition

Background: Cancer-associated fibroblasts (CAFs) support tumour progression and invasion, and they secrete abundant extracellular matrix (ECM) that may shield tumour cells from immune checkpoint or kinase inhibitors. Targeting CAFs using drugs that revert their differentiation, or inhibit their tumour-supportive functions, has been considered as an anti-cancer strategy. Methods: We have used human and murine cell culture models, atomic force microscopy (AFM), microarray analyses, CAF/tumour cell spheroid co-cultures and transgenic fibroblast reporter mice to study how targeting HDACs using small molecule inhibitors or siRNAs re-directs CAF differentiation and function in vitro and in vivo. Results: From a small molecule screen, we identified Scriptaid, a selective inhibitor of HDACs 1/3/8, as a repressor of TGFβ-mediated CAF differentiation. Scriptaid inhibits ECM secretion, reduces cellular contraction and stiffness, and impairs collective cell invasion in CAF/tumour cell spheroid co-cultures. Scriptaid also reduces CAF abundance and delays tumour growth in vivo. Conclusions: Scriptaid is a well-tolerated and effective HDACi that reverses many of the functional and phenotypic properties of CAFs. Impeding or reversing CAF activation/function by altering the cellular epigenetic regulatory machinery could control tumour growth and invasion, and be beneficial in combination with additional therapies that target cancer cells or immune cells directly

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Solitary pulse propagation in high gain optical fiber amplifiers with normal group velocity dispersion

Pulse propagation in high gain optical fiber amplifiers with normal group velocity dispersion is studied using numerical simulations of a generalized nonlinear Schrödinger equation including a complex Lorentzian gain profile. In particular, when the bandwidth of the input pulse is significantly less than that of the amplifier transition, an initial period of propagation where parabolic pulse characteristics are observed is followed by a solitary wave regime where the pulse temporal and spectral widths are stabilized by the limiting effect of the transition. The intensity and chirp characteristics of the resulting solitary pulse are considered in detail and dimensional analysis yields an empirical expression for the solitary wave peak power in excellent agreement with simulations