New approach in the treatment of ophthalmic neovascular disorders: using fusion protein aflibercept

The aim of this review is to appraise the usage of a newly approved anti-vascular endothelial growth factor (anti-VEGF) fusion protein, aflibercept, in ocular neovascular disorders such as diabetic retinopathy and age-related macular degeneration. Aflibercept is a soluble fusion protein, which combines ligand-binding elements taken from the extracellular domains of VEGF receptors 1 and 2 fused to the Fc portion of IgG. This protein contains all human amino acid sequences, which minimizes the risk for immunogenicity in human patients. In this short review we investigate the available literature and data from clinical studies on the efficacy, pharmaceutical and pharmacological properties of aflibercept, and identify its possible advantages over commercially available anti-VEGF drugs.Biomedical Reviews 2014; 25: 59-65

A universal form of slow dynamics in zero-temperature random-field Ising model

The zero-temperature Glauber dynamics of the random-field Ising model describes various ubiquitous phenomena such as avalanches, hysteresis, and related critical phenomena. Here, for a model on a random graph with a special initial condition, we derive exactly an evolution equation for an order parameter. Through a bifurcation analysis of the obtained equation, we reveal a new class of cooperative slow dynamics with the determination of critical exponents.Comment: 4 pages, 2 figure

Phase Transition in a Self-repairing Random Network

We consider a network, bonds of which are being sequentially removed; that is done at random, but conditioned on the system remaining connected (Self-Repairing Bond Percolation SRBP). This model is the simplest representative of a class of random systems for which forming of isolated clusters is forbidden. It qualitatively describes the process of fabrication of artificial porous materials and degradation of strained polymers. We find a phase transition at a finite concentration of bonds $p=p_c$, at which the backbone of the system vanishes; for all $p<p_c$ the network is a dense fractal.Comment: 4 pages, 4 figure

Optic disc melanocytoma associated with macular cyst

BACKGROUND: Optic disc melanocytoma (ODM) is a benign tumor, most often asymptomatic and stationary. However occasionally it can grow slowly, cause visual loss or extremely rarely undergoes into malignant melanoma. Here lies the importance of periodic ocular examination and reliable documentation.AIM: to report a rare case of growing ODM, associated with macular cyst with related visual loss, 25-years follow-up, and documentation by color photography, optical coherence tomography (OCT) and fluorescein angiography (FAG).METHODS: Full ophthalmic examination, fundus color photography, FAG and OCT.CASE REPORT: An asymptomatic 40-year-old Caucasian female with normal visual acuity at routine ocular examination had a pigmented elevated lesion on the left optic disc, occupying the inferotemporal half. The diagnosis of ODM was based on clinical assessment, FAG, fundus photographies, and observation was recommended. Ten years later she complained of gradually decreasing visual acuity in the left eye. Dilated ophthalmoscopy showed an evidence of slow growth of ODM and initial macular degeneration. After 25 years fundus color photography, FAG, and OCT documented mild progressive growth of ODM and macular cyst in the same eye.CONCLUSION: According to the literature, optic disc melanocytoma is generally recognized to be a stationary lesion with excellent prognosis and no treatment is usually necessary. In our case fundus color photography, FAG and OCT data reveal persisting ODM. Despite the progressive growth of ODM and moderate to significant visual loss, the malignant transformation is not proved. We suggest that loss of vision is related with macular lesion. To our knowledge we report a rare case of 25 years follow-up of growing ODM with visual loss, associated with macula degeneration/cyst.

The topological relationship between the large-scale attributes and local interaction patterns of complex networks

Recent evidence indicates that the abundance of recurring elementary interaction patterns in complex networks, often called subgraphs or motifs, carry significant information about their function and overall organization. Yet, the underlying reasons for the variable quantity of different subgraph types, their propensity to form clusters, and their relationship with the networks' global organization remain poorly understood. Here we show that a network's large-scale topological organization and its local subgraph structure mutually define and predict each other, as confirmed by direct measurements in five well studied cellular networks. We also demonstrate the inherent existence of two distinct classes of subgraphs, and show that, in contrast to the low-density type II subgraphs, the highly abundant type I subgraphs cannot exist in isolation but must naturally aggregate into subgraph clusters. The identified topological framework may have important implications for our understanding of the origin and function of subgraphs in all complex networks.Comment: pape

Minimum spanning trees on random networks

We show that the geometry of minimum spanning trees (MST) on random graphs is universal. Due to this geometric universality, we are able to characterise the energy of MST using a scaling distribution ($P(\epsilon)$) found using uniform disorder. We show that the MST energy for other disorder distributions is simply related to $P(\epsilon)$. We discuss the relationship to invasion percolation (IP), to the directed polymer in a random media (DPRM) and the implications for the broader issue of universality in disordered systems.Comment: 4 pages, 3 figure

Inverse Regulation of Inflammation and Mitochondrial Function in Adipose Tissue Defines Extreme Insulin Sensitivity in Morbidly Obese Patients

Obesity is associated with insulin resistance, a major risk factor for type 2 diabetes and cardiovascular disease. However, not all obese individuals are insulin resistant, which confounds our understanding of the mechanistic link between these conditions. We conducted transcriptome analyses on 835 obese subjects with mean BMI of 48.8, on which we have previously reported genetic associations of gene expression. Here, we selected ∼320 nondiabetic (HbA1c <7.0) subjects and further stratified the cohort into insulin-resistant versus insulin-sensitive subgroups based on homeostasis model assessment–insulin resistance. An unsupervised informatics analysis revealed that immune response and inflammation-related genes were significantly downregulated in the omental adipose tissue of obese individuals with extreme insulin sensitivity and, to a much lesser extent, in subcutaneous adipose tissue. In contrast, genes related to β-oxidation and the citric acid cycle were relatively overexpressed in adipose of insulin-sensitive patients. These observations were verified by querying an independent cohort of our published dataset of 37 subjects whose subcutaneous adipose tissue was sampled before and after treatment with thiazolidinediones. Whereas the immune response and inflammation pathway genes were downregulated by thiazolidinedione treatment, β-oxidation and citric acid cycle genes were upregulated. This work highlights the critical role that omental adipose inflammatory pathways might play in the pathophysiology of insulin resistance, independent of body weight

Measurement of an excess in the yield of J/ψ\psi at very low pTp_{\rm T} in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

We report on the first measurement of an excess in the yield of J/$\psi$ at very low transverse momentum ($p_{\rm T}< 0.3$ GeV/$c$) in peripheral hadronic Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 2.76 TeV, performed by ALICE at the CERN LHC. Remarkably, the measured nuclear modification factor of J/$\psi$ in the rapidity range $2.5<y<4$ reaches about 7 (2) in the $p_{\rm T}$ range 0-0.3 GeV/$c$ in the 70-90% (50-70%) centrality class. The J/$\psi$ production cross section associated with the observed excess is obtained under the hypothesis that coherent photoproduction of J/$\psi$ is the underlying physics mechanism. If confirmed, the observation of J/$\psi$ coherent photoproduction in Pb-Pb collisions at impact parameters smaller than twice the nuclear radius opens new theoretical and experimental challenges and opportunities. In particular, coherent photoproduction accompanying hadronic collisions may provide insight into the dynamics of photoproduction and nuclear reactions, as well as become a novel probe of the Quark-Gluon Plasma.Comment: 18 pages, 3 captioned figures, 1 table, authors from page 13, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/191

Coarse-Graining and Self-Dissimilarity of Complex Networks

Can complex engineered and biological networks be coarse-grained into smaller and more understandable versions in which each node represents an entire pattern in the original network? To address this, we define coarse-graining units (CGU) as connectivity patterns which can serve as the nodes of a coarse-grained network, and present algorithms to detect them. We use this approach to systematically reverse-engineer electronic circuits, forming understandable high-level maps from incomprehensible transistor wiring: first, a coarse-grained version in which each node is a gate made of several transistors is established. Then, the coarse-grained network is itself coarse-grained, resulting in a high-level blueprint in which each node is a circuit-module made of multiple gates. We apply our approach also to a mammalian protein-signaling network, to find a simplified coarse-grained network with three main signaling channels that correspond to cross-interacting MAP-kinase cascades. We find that both biological and electronic networks are 'self-dissimilar', with different network motifs found at each level. The present approach can be used to simplify a wide variety of directed and nondirected, natural and designed networks.Comment: 11 pages, 11 figure