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

Erratum: Flt3L dependence helps define an uncharacterized subset of murine cutaneous dendritic cells

[No abstract available

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

Flt3L dependence helps define an uncharacterized subset of murine cutaneous dendritic cells

Skin-derived dendritic cells (DCs) are potent antigen-presenting cells with critical roles in both adaptive immunity and tolerance to self. Skin DCs carry antigens and constitutively migrate to the skin-draining lymph nodes (LNs). In mice, Langerin-CD11b- dermal DCs are a low-frequency, heterogeneous, migratory DC subset that traffics to LNs (Langerin-CD11b- migDCs). Here, we build on the observation that Langerin-CD11b- migDCs are Fms-like tyrosine kinase 3 ligand (Flt3L) dependent and strongly Flt3L responsive, which may relate them to classical DCs. Examination of DC capture of FITC from painted skin, DC isolation from skin explant culture, and from the skin of CCR7 knockout mice, which accumulate migDCs, demonstrate these cells are cutaneous residents. Langerin-CD11b- Flt3L-responsive DCs are largely CD24(+) and CX 3 CR1 low and can be depleted from Zbtb46-DTR mice, suggesting classical DC lineage. Langerin-CD11b- migDCs present antigen with equal efficiency to other DC subsets ex vivo, including classical CD8α cDCs and Langerin+CD103+ dermal DCs. Finally, transcriptome analysis suggests a close relationship with other skin DCs, and a lineage relationship with other classical DCs. This work demonstrates that Langerin- CD11b- dermal DCs, a previously overlooked cell subset, may be an important contributor to the cutaneous immune environment

Elliptic flow at high transverse momentum in Pb-Pb collisions at sNN=2.76\sqrt{s_{NN}} = 2.76 TeV with the ALICE experiment

An observable that can be used to better constrain the mechanism responsible for the parton energy loss is the elliptic azimuthal event anisotropy, $v_2$. We report on measurements of $v_2$ for inclusive and identified charged particles in Pb-Pb collisions at $\sqrt{s_{NN}} = 2.76$ TeV recorded by the ALICE experiment at the LHC. $v_2$ is presented for a wide range of particle transverse momentum up to $p_T=20$ GeV/c. The particle $v_2$ is finite, positive and approximately constant for $p_T>8$ GeV/c. The proton $v_2$ is higher than that of the pion up to about $p_T=8$ GeV/c. The results are compared to the measurements at lower energy reported by RHIC experiments.Comment: 4 pages, QM 2011 proceeding

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.

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

Elliptical stretch as a cause of side branch ostial compromise after main vessel stenting in coronary bifurcations: New insights from numerical analysis

Background: The side branch (SB) compromise after main vessel (MV) stenting remains a significant problem in coronary bifurcation treatment. Currently the two major hypotheses for the mechanism of SB compromise are carina shift from MV into the SB and plaque shift into the ostium of side vessel. It is proposed herein, SB ostial deformation leading to reshaping of the ostium from circle to ellipse is a third possible mechanism. In the current study, the theoretical effects and correlation of ostial deformation with fractional flow reserve (FFR) is explored.Methods: Based on angiographic measurements and theoretical analysis formulas, three different SB ostial areas using circular ostial shape assumption and elliptical ostial shape assumption were calculated. Three different types of ostial areas with FFR values after MV stenting in 49 patients from the FIESTA registry were compared and analyzed.Results: It was found that there is significant overestimation of stenosis severity when estimated by the circle formula, than with the ellipse formula — ASc vs. ASds with 25% ± 13%, p &lt; 0.001, ASc vs. ASmld with 9% ± 10%, p &lt; 0.001. The elliptical shape assumptions provide more accurate ostial area stenosis, which correlates better with FFR. This finding is more significant in less severe stenosis (&lt; 70% area stenosis) than in a more severe one.Conclusions: A third possible mechanism of SB compromise after MV stenting of coronary bifurcation stenosis is elliptical ostial deformation at the ostium of SBs. The ostial area, calculated based on elliptical assumption correlates better with FFR, than area stenosis calculated with the traditional circular formula