A Case of Choroidal Neovascularization Secondary to Unilateral Retinal Pigment Epithelium Dysgenesis

Aim: To report a case of choroidal neovascularization secondary to unilateral retinal pigment epithelium dysgenesis (URPED), which was resistant to posterior subtenon injection of triamcinolone acetonide (STTA) and intravitreal bevacizumab injection (IVB). Case Report: An 8-year-old boy was referred to us because of a unilateral unique clinical appearance on funduscopic examination in his left eye (OS). A geometric lesion at the retinal pigment epithelium level of the interpapillomacular area was disclosed OS. The optic nerve was slightly hyperemic OS. Findings from the right fundus examination were normal. Based on these characteristic findings, he was diagnosed as having URPED. Best corrected Landolt ring chart visual acuity (BCVA) was 1.0 in both eyes. Twenty-three months after the first visit, the patient presented with visual disturbance OS. Funduscopic examination showed an expansion of the geometric lesion and the development of a subfoveal choroidal neovascularization (CNV). BCVA was 0.4 OS. Two-time STTA (40 mg/1 ml) was performed at the onset of CNV and 6 months later, and additional IVB (1.25 mg/0.05 ml) was done 10 months later for the treatment of CNV, but the geometric lesion and CNV were resistant to the treatment and continued to expand. Seven years after the first visit, the geometric lesion and the CNV kept expanding steadily. Conclusion: URPED is a rare clinical entity, and the prognosis of this disease is still unclear. The visual prognosis may depend on whether CNV fully develops

Macular Edema Formation and Deterioration of Retinal Function after Intravitreal Bevacizumab Injection for Proliferative Diabetic Retinopathy

Purpose: To report a case of proliferative diabetic retinopathy (PDR) showing transient macular edema (ME) and deteriorated retinal function after intravitreal bevacizumab injection (IVB). Methods and Results: A 53-year-old man received IVB (1.25 mg/0.05 ml) in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+) in the anterior chamber in both eyes. Optical coherence tomography showed ME formation in the left eye. Both full-field and multifocal electroretinography (ERG) revealed the deterioration of all parameters in both eyes compared with pretreatment. The inflammation in the anterior segment and ME disappeared 1 day after the injection. ERG parameters were improved 9 days after the injection, except for the N1 and P1 amplitude of multifocal ERG in the left eye. Conclusion: We propose that patients who undergo IVB should be carefully informed and followed up for possible complications including temporal ME formation and retinal function deterioration

A Case of Bilateral Macular Holes Showing Onset and Spontaneous Closure over Very Short Intervals

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Elastic Scalable Cloud Computing Using Application-Level Migration

middleware framework to support autonomous workload elas-ticity and scalability based on application-level migration as a reconfiguration strategy. While other scalable frameworks (e.g., MapReduce or Google App Engine) force application developers to write programs following specific APIs, COS provides scal-ability in a general-purpose programming framework based on an actor-oriented programming language. When all executing VMs are highly utilized, COS scales a workload up by migrating mobile actors over to newly dynamically created VMs. When VM utilization drops, COS scales the workload down by consolidating actors and terminating idle VMs. Application-level migration is advantageous compared to VM migration especially in hybrid clouds in which migration costs over the Internet are critical to scale out the workloads. We demonstrate the general purpose programming approach using a tightly-coupled computation. We compare the performance of autonomous (i.e., COS-driven) versus ideal reconfiguration, as well as the impact of granularity of reconfiguration, i.e., VM migration versus application-level migration. Our results show promise for future fully automated cloud computing resource management systems that efficiently enable truly elastic and scalable general-purpose workloads. I

Carbon-Ion Irradiation Suppresses Migration and Invasiveness of Human Pancreatic Carcinoma Cells MIAPaCa-2 via Rac1 and RhoA Degradation

PurposeTo investigate the mechanisms underlying the inhibition of cancer cell migration and invasion by carbon (C)-ion irradiation.Methods and MaterialsHuman pancreatic cancer cells MIAPaCa-2, AsPC-1, and BxPC-3 were treated by x-ray (4 Gy) or C-ion (0.5, 1, 2, or 4 Gy) irradiation, and their migration and invasion were assessed 2 days later. The levels of guanosine triphosphate (GTP)-bound Rac1 and RhoA were determined by the active GTPase pull-down assay with or without a proteasome inhibitor, and the binding of E3 ubiquitin ligase to GTP-bound Rac1 was examined by immunoprecipitation.ResultsCarbon-ion irradiation reduced the levels of GTP-bound Rac1 and RhoA, 2 major regulators of cell motility, in MIAPaCa-2 cells and GTP-bound Rac1 in AsPC-1 and BxPC-3 cells. Proteasome inhibition reversed the effect, indicating that C-ion irradiation induced Rac1 and RhoA degradation via the ubiquitin (Ub)-proteasome pathway. E3 Ub ligase X-linked inhibitor of apoptosis protein (XIAP), which directly targets Rac1, was selectively induced in C-ion–irradiated MIAPaCa-2 cells and coprecipitated with GTP-bound Rac1 in C-ion–irradiated cells, which was associated with Rac1 ubiquitination. Cell migration and invasion reduced by C-ion radiation were restored by short interfering RNA–mediated XIAP knockdown, indicating that XIAP is involved in C-ion–induced inhibition of cell motility.ConclusionIn contrast to x-ray irradiation, C-ion treatment inhibited the activity of Rac1 and RhoA in MIAPaCa-2 cells and Rac1 in AsPC-1 and BxPC-3 cells via Ub-mediated proteasomal degradation, thereby blocking the motility of these pancreatic cancer cells

Double knockdown of α1,6-fucosyltransferase (FUT8) and GDP-mannose 4,6-dehydratase (GMD) in antibody-producing cells: a new strategy for generating fully non-fucosylated therapeutic antibodies with enhanced ADCC

<p>Abstract</p> <p>Background</p> <p>Antibody-dependent cellular cytotoxicity (ADCC) is greatly enhanced by the absence of the core fucose of oligosaccharides attached to the Fc, and is closely related to the clinical efficacy of anticancer activity in humans <it>in vivo</it>. Unfortunately, all licensed therapeutic antibodies and almost all currently-developed therapeutic antibodies are heavily fucosylated and fail to optimize ADCC, which leads to a large dose requirement at a very high cost for the administration of antibody therapy to cancer patients. In this study, we explored the possibility of converting already-established antibody-producing cells to cells that produce antibodies fully lacking core fucosylation in order to facilitate the rapid development of next-generation therapeutic antibodies.</p> <p>Results</p> <p>Firstly, loss-of-function analyses using small interfering RNAs (siRNAs) against the three key genes involved in oligosaccharide fucose modification, i.e. α1,6-fucosyltransferase (<it>FUT8</it>), GDP-mannose 4,6-dehydratase (<it>GMD</it>), and GDP-fucose transporter (<it>GFT</it>), revealed that single-gene knockdown of each target was insufficient to completely defucosylate the products in antibody-producing cells, even though the most effective siRNA (>90% depression of the target mRNA) was employed. Interestingly, beyond our expectations, synergistic effects of <it>FUT8 </it>and <it>GMD </it>siRNAs on the reduction in fucosylation were observed, but not when these were used in combination with <it>GFT </it>siRNA. Secondly, we successfully developed an effective short hairpin siRNA tandem expression vector that facilitated the double knockdown of <it>FUT8 </it>and <it>GMD</it>, and we converted antibody-producing Chinese hamster ovary (CHO) cells to fully non-fucosylated antibody producers within two months, and with high converting frequency. Finally, the stable manufacture of fully non-fucosylated antibodies with enhanced ADCC was confirmed using the converted cells in serum-free fed-batch culture.</p> <p>Conclusion</p> <p>Our results suggest that FUT8 and GMD collaborate synergistically in the process of intracellular oligosaccharide fucosylation. We also demonstrated that double knockdown of <it>FUT8 </it>and <it>GMD </it>in antibody-producing cells could serve as a new strategy for producing next-generation therapeutic antibodies fully lacking core fucosylation and with enhanced ADCC. This approach offers tremendous cost- and time-sparing advantages for the development of next-generation therapeutic antibodies.</p

Inhomogeneous superconductivity in thin crystals of FeSe1-xTex (x=1.0, 0.95, and 0.9)

We investigated the temperature dependence of resistivity in thin crystals of FeSe1-xTex (x = 1.0, 0.95, and 0.9), though bulk crystals with 1.0 x 0.9 are known to be non-superconducting. With decreasing thickness of the crystals, the resistivity of x = 0.95 and 0.9 decreases and reaches zero at a low temperature, which indicates a clear superconducting transition. The anomaly of resistivity related to the structural and magnetic transitions completely disappears in 55- to 155-nm-thick crystals of x = 0.9, resulting in metallic behavior in the normal state. Microbeam x-ray diffraction measurements were performed on bulk single crystals and thin crystals of FeSe1-xTex. A significant difference of the lattice constant, c, was observed in FeSe1-xTex, which varied with differing Te content (x), and even in crystals with the same x, which was mainly caused by inhomogeneity of the Se/Te distribution. It has been found that the characteristic temperatures causing the structural and magnetic transition (T-t), the superconducting transition (T-c), and the zero resistivity (T-c(zero)) are closely related to the value of c in thin crystals of FeSe1-xTex