Correlation from undiluted vitreous cytokines of untreated central retinal vein occlusion with spectral domain optical coherence tomography

Purpose: To correlate inflammatory and proangiogenic key cytokines from undiluted vitreous of treatment-naïve central retinal vein occlusion (CRVO) patients with SD-OCT parameters. Methods: Thirty-five patients (age 71.1 years, 24 phakic, 30 nonischemic) underwent intravitreal combination therapy, including a single-site 23-gauge core vitrectomy. Twenty-eight samples from patients with idiopathic, non-uveitis floaterectomy served as controls. Interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF-A) levels were correlated with the visual acuity (logMar), category of CRVO (ischemic or nonischemic) and morphologic parameters, such as central macular thickness-CMT, thickness of neurosensory retina-TNeuro, extent of serous retinal detachment-SRT and disintegrity of the IS/OS and others. Results: The mean IL-6 was 64.7pg/ml (SD ± 115.8), MCP-1 1015.7 ( ± 970.1), and VEGF-A 278.4 ( ± 512.8), which was significantly higher than the control IL-6 6.2 ± 3.4pg/ml (P=0.06), MCP-1 253.2 ± 73.5 (P<0.0000001) and VEGF-A 7.0 ± 4.9 (P<0.0006). All cytokines correlated highly with one another (correlation coefficient r=0.82 for IL-6 and MCP-1; r=0.68 for Il-6 and VEGF-A; r=0.64 for MCP-1 and VEGF-A). IL-6 correlated significantly with CMT, TRT, SRT, dIS/OS, and dELM. MCP-1 correlated significantly with SRT, dIS/OS, and dELM. VEGF-A correlated not with changes in SD-OCT, while it had a trend to be higher in the ischemic versus the nonischemic CRVO group (P=0.09). Conclusions: The inflammatory cytokines were more often correlated with morphologic changes assessed by SD-OCT, whereas VEGF-A did not correlate with CRVO-associated changes in SD-OCT. VEGF inhibition alone may not be sufficient in decreasing the inflammatory response in CRVO therapy

RHEBI Expression in Embryonic and Postnatal Mouse

Ras homolog enriched in brain (RHEB1) is a member within the superfamily of GTP-binding proteins encoded by the RAS oncogenes. RHEB1 is located at the crossroad of several important pathways including the insulin-signaling pathways and thus plays an important role in different physiological processes. To understand better the physiological relevance of RHEB1 protein, the expres- sion pattern of RHEB1 was analyzed in both embryonic (at E3.5–E16.5) and adult (1-month old) mice. RHEB1 immu- nostaining and X-gal staining were used for wild-type and Rheb1 gene trap mutant mice, respectively. These inde- pendent methods revealed similar RHEB1 expression pat- terns during both embryonic and postnatal developments. Ubiquitous uniform RHEB1/β-gal and/or RHEB1 expres- sion was seen in preimplantation embryos at E3.5 and post- implantation embryos up to E12.5. Between stages E13.5 and E16.5, RHEB1 expression levels became complex: In particular, strong expression was identified in neural tis- sues, including the neuroepithelial layer of the mesenceph- alon, telencephalon, and neural tube of CNS and dorsal root ganglia. In addition, strong expression was seen in certain peripheral tissues including heart, intestine, muscle, and urinary bladder. Postnatal mice have broad spatial RHEB1 expression in different regions of the cerebral cortex, sub- cortical regions (including hippocampus), olfactory bulb, medulla oblongata, and cerebellum (particularly in Purkinje cells). Significant RHEB1 expression was also viewed in internal organs including the heart, intestine, urinary blad- der, and muscle. Moreover, adult animals have complex tis- sue- and organ-specific RHEB1 expression patterns with different intensities observed throughout postnatal develop- ment. Its expression level is in general comparable in CNS and other organs of mouse. Thus, the expression pattern of RHEB1 suggests that it likely plays a ubiquitous role in the development of the early embryo with more tissue-specific roles in later development

Universal manifold pairings and positivity

Gluing two manifolds M_1 and M_2 with a common boundary S yields a closed manifold M. Extending to formal linear combinations x=Sum_i(a_i M_i) yields a sesquilinear pairing p= with values in (formal linear combinations of) closed manifolds. Topological quantum field theory (TQFT) represents this universal pairing p onto a finite dimensional quotient pairing q with values in C which in physically motivated cases is positive definite. To see if such a "unitary" TQFT can potentially detect any nontrivial x, we ask if is non-zero whenever x is non-zero. If this is the case, we call the pairing p positive. The question arises for each dimension d=0,1,2,.... We find p(d) positive for d=0,1, and 2 and not positive for d=4. We conjecture that p(3) is also positive. Similar questions may be phrased for (manifold, submanifold) pairs and manifolds with other additional structure. The results in dimension 4 imply that unitary TQFTs cannot distinguish homotopy equivalent simply connected 4-manifolds, nor can they distinguish smoothly s-cobordant 4-manifolds. This may illuminate the difficulties that have been met by several authors in their attempts to formulate unitary TQFTs for d=3+1. There is a further physical implication of this paper. Whereas 3-dimensional Chern-Simons theory appears to be well-encoded within 2-dimensional quantum physics, eg in the fractional quantum Hall effect, Donaldson-Seiberg-Witten theory cannot be captured by a 3-dimensional quantum system. The positivity of the physical Hilbert spaces means they cannot see null vectors of the universal pairing; such vectors must map to zero.Comment: Published by Geometry and Topology at http://www.maths.warwick.ac.uk/gt/GTVol9/paper53.abs.htm

RHEB1 Expression in Embryonic and Postnatal Mouse

Ras homolog enriched in brain (RHEB1) is a member within the superfamily of GTP-binding proteins encoded by the RAS oncogenes. RHEB1 is located at the crossroad of several important pathways including the insulin-signaling pathways and thus plays an important role in different physiological processes. To understand better the physiological relevance of RHEB1 protein, the expres-sion pattern of RHEB1 was analyzed in both embryonic (at E3.5–E16.5) and adult (1-month old) mice. RHEB1 immu-nostaining and X-gal staining were used for wild-type and Rheb1 gene trap mutant mice, respectively. These inde-pendent methods revealed similar RHEB1 expression pat-terns during both embryonic and postnatal developments. Ubiquitous uniform RHEB1/β-gal and/or RHEB1 expres-sion was seen in preimplantation embryos at E3.5 and post-implantation embryos up to E12.5. Between stages E13.5 and E16.5, RHEB1 expression levels became complex: In particular, strong expression was identified in neural tis-sues, including the neuroepithelial layer of the mesenceph-alon, telencephalon, and neural tube of CNS and dorsal root ganglia. In addition, strong expression was seen in certain peripheral tissues including heart, intestine, muscle, and urinary bladder. Postnatal mice have broad spatial RHEB1 expression in different regions of the cerebral cortex, sub-cortical regions (including hippocampus), olfactory bulb, medulla oblongata, and cerebellum (particularly in Purkinje cells). Significant RHEB1 expression was also viewed in internal organs including the heart, intestine, urinary blad-der, and muscle. Moreover, adult animals have complex tis-sue- and organ-specific RHEB1 expression patterns with different intensities observed throughout postnatal develop-ment. Its expression level is in general comparable in CNS and other organs of mouse. Thus, the expression pattern of RHEB1 suggests that it likely plays a ubiquitous role in the development of the early embryo with more tissue-specific roles in later development

Self-Assembly of Core-Shell Hybrid Nanoparticles by Directional Crystallization of Grafted Polymers

Nanoparticle self-assembly is an efficient bottom-up strategy for the creation of nanostructures. In the standard approach, ligands are grafted on the surfaces of nanoparticles to keep them separated and control interparticle interactions. Ligands then remain secondary and usually are not expected to order significantly during superstructure formation. Here, we investigate how ligands can play a more primary role in the formation of inorganic-organic hybrid materials. We graft poly(2-iso-propyl-2-oxazoline) (PiPrOx) as a crystallizable shell onto SiO$_2$ nanoparticles. By varying the PiPrOx grafting density, solution stability, and nanoparticle aggregation behavior can be controlled. Upon prolonged heating, anisotropic nanostructures form in conjunction with the crystallization of the ligands. Self-assembly of hybrid PiPrOx@SiO$_2$ (shell@core) nanoparticles proceeds in two steps: First, rapid formation of amorphous aggregates via gelation, mediated by the interaction between nanoparticles through grafted polymers; second, slow radial growth of fibers via directional crystallization, governed by the incorporation of crystalline ribbons formed from unbound polymers coupling to the grafted polymer shell. Our work reveals how crystallization-driven self-assembly of ligands can create intricate hybrid nanostructures.Comment: 12 pages, 5 figure

Evidence for electronically-driven ferroelectricity in the family of strongly correlated dimerized BEDT-TTF molecular conductors

By applying measurements of the dielectric constants and relative length changes to the dimerized molecular conductor $\kappa$-(BEDT-TTF)$_2$Hg(SCN)$_2$Cl, we provide evidence for order-disorder type electronic ferroelectricity which is driven by charge order within the (BEDT-TTF)$_2$ dimers and stabilized by a coupling to the anions. According to our density functional theory calculations, this material is characterized by a moderate strength of dimerization. This system thus bridges the gap between strongly dimerized materials, often approximated as dimer-Mott systems at 1/2 filling, and non- or weakly dimerized systems at 1/4 filling exhibiting charge order. Our results indicate that intra-dimer charge degrees of freedom are of particular importance in correlated $\kappa$-(BEDT-TTF)$_2$X salts and can create novel states, such as electronically-driven multiferroicity or charge-order-induced quasi-1D spin liquids.Comment: 6 pages, 4 figures + Supplementary Information (8 pages, 8 figures

Probabilistic Evacuation Assessment with Real-time Monitoring Information

The present paper proposes a probabilistic modeling approach for assessment and decision support of tactical loss reduction for roadway tunnel systems subject to fire events. The proposed probabilistic modeling approach combines scenario-based risk models for the probabilistic representation of accidents and fires with agent-based probabilistic representations of the escape scenarios of persons. The Fehmarn-belt tunnel is used as case study and a real-time daily traffic (RTDT) curve is considered. The vehicle population and the number and categories of persons in individual vehicles are modelled probabilistically based on statistics from the European Union. The example focuses on the modelling and assessment of the effects of tunnel closure, as a risk reducing measure in case of fire, on the evacuation dynamics. The results show that fast hindrance of traffic entry into the tunnel system efficiently reduces the expected value of the number of exposed persons but at the same time increases the variance associated with the number of persons evacuated within a given time frame.This work is part of Femern SafetyLab Project, funded by the Danish Agency for Science and Higher Education