Factors associated with extended remission in neovascular age-related macular degeneration on pro re nata treatment protocol.

AimTo show the characteristics and outcomes of patients with neovascular age-related macular degeneration (nAMD) who had extended remission (ER) while on a pro re nata (PRN) treatment protocol.MethodsThis was a retrospective case-control study of a consecutive series of patients with nAMD treated with a PRN antivascular endothelial growth factor (anti-VEGF) drug regimen. ER was defined as the absence of haemorrhage, intraretinal/subretinal fluid on optical coherence tomography and leakage on fluorescein angiography for 52 weeks after cessation of anti-VEGF therapy. Matching patients with nAMD who did not achieve ER were included as control group. Cox regression analysis was fitted to identify predictors of time to achieve ER and time to recurrence. A logistic regression analysis of baseline characteristics was used to identify predictors of achieving ER.ResultsOf 830 eyes treated with anti-VEGF monotherapy, 77 (9.2%) eyes achieved ER during a median follow-up of 236 weeks (range 70-525 weeks). Cox regression analysis showed that ER was achieved earlier in eyes with isolated intraretinal fluid (HR, 2.05; 95% CI 1.929 to 4.520; p=0.045) at presentation. Logistic regression analysis showed that type 3 choroidal neovascularisation (OR, 0.090; 95% CI 0.021 to 0.382; p=0.001), thinner choroid (OR, 0.993; 95% CI 0.988 to 0.998; p=0.004) and absence of macular atrophy (OR, 0.233; 95% CI 0.065 to 0.839; p=0.026) at baseline increased the likelihood of achieving ER.ConclusionER is achievable in 9.2% of patients under PRN therapy for nAMD. At presentation with nAMD, anatomical features on retinal imaging may predict the likelihood of achieving ER and a shorter time to achieve ER

[11C]Carbon Dioxide: Starting Point for Labeling PET Radiopharmaceuticals

Positron emission tomography (PET) is a powerful in vivo imaging technique capable of providing dynamic information on biochemical processes in the living human subject. Applications of PET in oncology, neurology, psychiatry, cardiology and other medical specialties continue to grow. The use of PET relies on the characteristics and availability of appropriately labeled radiopharmaceuticals. Carbon-11 is one of the most useful radionuclides for PET chemistry, since its introduction into a biologically active molecule dose not modify the biochemical properties of the compound. [11C]Carbon dioxide (11CO2), produced by cyclotron, is the most common and versatile primary labeling precursor in the production of 11C–labeled radiopharmaceuticals

Influences of luminance contrast and ambient lighting on visual context learning and retrieval

Invariant spatial context can guide attention and facilitate visual search, an effect referred to as “contextual cueing.” Most previous studies on contextual cueing were conducted under conditions of photopic vision and high search item to background luminance contrast, leaving open the question whether the learning and/or retrieval of context cues depends on luminance contrast and ambient lighting. Given this, we conducted three experiments (each contains two subexperiments) to compare contextual cueing under different combinations of luminance contrast (high/low) and ambient lighting (photopic/mesopic). With high-contrast displays, we found robust contextual cueing in both photopic and mesopic environments, but the acquired contextual cueing could not be transferred when the display contrast changed from high to low in the photopic environment. By contrast, with low-contrast displays, contextual facilitation manifested only in mesopic vision, and the acquired cues remained effective following a switch to high-contrast displays. This pattern suggests that, with low display contrast, contextual cueing benefited from a more global search mode, aided by the activation of the peripheral rod system in mesopic vision, but was impeded by a more local, fovea-centered search mode in photopic vision

Xylella fastidiosa pil-chp operon is involved in regulating key structural genes of both type I and IV pili

Xylella fastidiosa is the causal agent of Pierce's disease (PD) in grapevines. It has type I and type IV pili, which are both virulence factors involved in the PD-associated processes of motility, aggregation, and biofilm formation. Many questions remain as to how the two pili are regulated. We previously identified a X. fastidiosa pil-chp chemosensory-like cluster as an operon composed of genes pilG-I-J-L-chpB-C. In this study, we deleted pilG (resulting in a ∆pilG-I strain) and pilJ and discovered that both mutants (∆pilG-I and ∆pilJ) had reduced virulence after 24 weeks post-inoculation, whereas ∆chpB and ∆chpC did not. Both ∆pilG-I and ∆pilJ lost motility and were impaired in biofilm formation in rich artificial media and xylem sap. Gene expression was significantly downregulated for representative fimbrial adhesin and motility genes in ∆pilG-I, and to a lesser extent in ∆pilJ. Our data suggest that Pil, but not Chp, proteins are virulence factors, and pilG-I-J are involved in transcriptional regulation of type I and IV pili virulence genes and therefore motility and biofilm formation. To our knowledge, this is the first report of a chemotaxis-like operon involved in the regulation of key structural genes of both type I and type IV pili

Effect of writing beam spatial coherence on fiber bragg grating modulation contrast and thermal stability

We present a method to fabricate fiber Bragg gratings with adjustable refractive index contrast by using the standard phase mask technique. A theoretical analysis of the diffracted field from the phase mask is performed by considering the effect of the spatial coherence of the incident UV beam. The numerical results show that the grating index contrast decreases as the separation between the fiber and the phase mask increases. Strong gratings with various index contrasts have been inscribed in hydrogen-loaded single mode fibers at different writing distances, and the measured index contrast values are in good agreement with the simulation results. Furthermore, thermal decay tests on the gratings demonstrate that the thermal stability of the grating reflectivity is improved for those gratings fabricated at larger separations between the fiber and the phase mask. These results suggest a one-step process to fabricate gratings with an enhanced thermal stability

Neutralizing the anticoagulant activity of ultra-low-molecular-weight heparins using N -acetylglucosamine 6-sulfatase

Heparin has been the most commonly used anticoagulant drug for nearly a century. The drug heparin is generally categorized into three forms according to its molecular weight (MW), unfractionated (UF, average MW 13,000), low molecular weight (LMW, average MW 5,000), and ultra-low molecular weight heparin (ULMWH, average MW 2,000). Overdose of anticoagulant heparin can lead to very dangerous bleeding in patients. Protamine sulfate can be administered as an antidote to reverse heparin’s anticoagulant effect. There is not an effective antidote for ULMWH. In the current study, we examine human N-acetylglucosamine 6-sulfatase (NG6S), expressed in Chinese hamster ovary cells as a reversal agent for ULMWH. NG6S removes a single 6-O-sulfo group at the non-reducing end of the ULMWH Arixtra® (fondaparinux) effectively removing its ability to bind to antithrombin and preventing its inhibition of coagulation factor Xa. These results pave the way to develop human NG6S as an antidote for neutralizing the anticoagulant activity of ULMWHs

Genipin-cross-linked collagen/chitosan biomimetic scaffolds for articular cartilage tissue engineering applications

This was the first study to use genipin to cross-link collagen and chitosan.In this study, genipin-cross-linked collagen/chitosan biodegradable porous scaffolds were prepared for articular cartilage regeneration. The influence of chitosan amount and genipin concentration on the scaffolds physicochemical properties was evaluated. The morphologies of the scaffolds were characterized by scanning electron microscope (SEM) and cross-linking degree was investigated by ninhydrin assay. Additionally, the mechanical properties of the scaffolds were assessed under dynamic compression. To study the swelling ratio and the biostability of the collagen/chitosan scaffold, in vitro tests were also carried out by immersion of the scaffolds in PBS solution or digestion in collagenase, respectively. The results showed that the morphologies of the scaffolds underwent a fiber-like to a sheet-like structural transition by increasing chitosan amount. Genipin cross-linking remarkably changed the morphologies and pore sizes of the scaffolds when chitosan amount was less than 25%. Either by increasing the chitosan ratio or performing cross-linking treatment, the swelling ratio of the scaffolds can be tailored. The ninhydrin assay demonstrated that the addition of chitosan could obviously increase the cross-linking efficiency. The degradation studies indicated that genipin cross-linking can effectively enhance the biostability of the scaffolds. The biocompatibility of the scaffolds was evaluated by culturing rabbit chondrocytes in vitro. This study demonstrated that a good viability of the chondrocytes seeded on the scaffold was achieved. The SEM analysis has revealed that the chondrocytes adhered well to the surface of the scaffolds and contacted each other. These results suggest that the genipin-cross-linked collagen/chitosan matrix may be a promising formulation for articular cartilage scaffolding.Key Projects in the National Science and Technology Pillar Program in the Eleventh Five-year Plan Period. Grant Number: 2006BA116B04Guangdong Natural Science Foundation. Grant Number: 07300602Natural Science Foundation Team Project of Guangdong. Grant Number: 4205786State Key Program of National Natural Science of China. Grant Number: 50732003National Basic Research Program of China. Grant Number: 2005CB62390

Toward the chemoenzymatic synthesis of heparan sulfate oligosaccharides: oxidative cleavage of p-nitrophenyl group with ceric ammonium salts

We have developed an efficient chemoenzymatic synthesis of heparan sulfate oligosaccharides employing the para-nitrophenyl (p-NP) β-glucuronide as an acceptor compatible with enzymatic elongation and one that significantly simplifies oligosaccharide purification on C-18 resin. Employing ceric ammonium nitrate as oxidative reagent to remove the p-NP group unexpectedly also removed the glucuronic acid residue at the reducing-end, affording a smaller oligosaccharide. The application of ceric ammonium sulfate allowed the removal of the p-NP without concomitant loss of the adjacent glucuronic acid offering a route to longer heparin sulfate oligosaccharide products

Regional innovation and spillover effects of foreign direct investment in China: a threshold approach

Using a data set on twenty-nine Chinese provinces for the period 1985–2008, this paper establishes a threshold model to analyse the relationship between spillover effects of foreign direct investment (FDI) and regional innovation in China. There is clear evidence of double-threshold effects of regional innovation on productivity spillovers from FDI. Specifically, only when the level of regional innovation reaches the minimum innovation threshold will FDI in the region begin to produce positive productivity spillovers. Furthermore, positive productivity spillovers from FDI will be substantial only when the level of regional innovation attains a higher threshold. The double threshold divides Chinese provinces into three super-regions in terms of innovation, with most provinces positioned within the middle-level innovation super-region. Policy implications are discussed

Heparan Sulfate Domains Required for Fibroblast Growth Factor 1 and 2 Signaling through Fibroblast Growth Factor Receptor 1c

A small library of well defined heparan sulfate (HS) polysaccharides was chemoenzymatically synthesized and used for a detailed structure-activity study of fibroblast growth factor (FGF) 1 and FGF2 signaling through FGF receptor (FGFR) 1c. The HS polysaccharide tested contained both undersulfated (NA) domains and highly sulfated (NS) domains as well as very well defined non-reducing termini. This study examines differences in the HS selectivity of the positive canyons of the FGF12-FGFR1c2 and FGF22-FGFR1c2 HS binding sites of the symmetric FGF2-FGFR2-HS2 signal transduction complex. The results suggest that FGF12-FGFR1c2 binding site prefers a longer NS domain at the non-reducing terminus than FGF22-FGFR1c2. In addition, FGF22-FGFR1c2 can tolerate an HS chain having an N-acetylglucosamine residue at its non-reducing end. These results clearly demonstrate the different specificity of FGF12-FGFR1c2 and FGF22-FGFR1c2 for well defined HS structures and suggest that it is now possible to chemoenzymatically synthesize precise HS polysaccharides that can selectively mediate growth factor signaling. These HS polysaccharides might be useful in both understanding and controlling the growth, proliferation, and differentiation of cells in stem cell therapies, wound healing, and the treatment of cancer