Using angle-selective optical film to enhance the light extraction of a thin-film encapsulated 3D reflective pixel for OLED displays.

Light extraction improvement is still an important issue for active-matrix organic light-emitting diode displays (AMOLEDs). In our previous work, a three-dimensional (3D) reflective pixel configuration embedding the OLED in the concave 3D reflector and patterned high-index filler had been proposed for significant enhancement of the pixel light extraction. In this work, influences of thin film encapsulation (TFE) on light extraction of such reflective 3D OLED pixels are considered as well by simulation studies. Unfortunately, the optical simulation reveals strong reduction of the light extraction efficiency induced by TFE layers. As such, an additional angle-selective optical film structure between the pixel and the encapsulation layers is introduced to control the angular distribution of the light coupled into the encapsulation layers and to solve TFE-induced optical losses. As a result, TFE-induced losses can be substantially reduced to retain much of light extraction efficiency. The results of this study are believed to provide useful insights and guides for developing even more efficient and power-saving AMOLEDs.

Nanoscale plasmonic wires with maximal figure of merits as a superior flexible transparent conducting electrode for RGB colors.

Based on incredibly increasing applications in modern optoelectronic devices, the demand for securing a superior conductive transparent electrode (TCE) candidate becomes significant and urgent. However, boosting both transmittance and conductance simultaneously is an intrinsic limitation. In this work, we present silver nanoscale plasmonic wires (Ag NPWs) to function as TCEs in the visible light region by lowering their corresponding plasma frequencies. By carefully designing geometric dimensions of the Ag NPWs, we also optimize the performance for red, green, and blue colors, respectively. The demonstrated figure of merits for RGB colors appeared respectively 443.29, 459.46, and 133.78 in simulation and 302.75, 344.11, and 348.02 in experiments. Evidently, our Ag NPWs offer much greater FoMs beyond conventional TCEs that are most frequently comprised of indium tin oxide and show further advantages of flexibility and less Moire effect for the applications of flexible and high-resolution optoelectronic devices.

Shear stress-induced atherosclerotic plaque composition in ApoE(-/-) mice is modulated by connexin37.

OBJECTIVE: Shear stress patterns influence atherogenesis and plaque stability; low laminar shear stress (LLSS) promotes unstable plaques whereas oscillatory shear stress (OSS) induces more stable plaques. Endothelial connexin37 (Cx37) expression is also regulated by shear stress, which may contribute to localization of atherosclerotic disease. Moreover, Cx37 reduces initiation of atherosclerosis by inhibiting monocyte adhesion. The present work investigates the effect of Cx37 on the phenotype of plaques induced by LLSS or OSS. METHODS: Shear stress-modifying casts were placed around the common carotid artery of ApoE(-/-) or ApoE(-/-)Cx37(-/-) mice, and animals were placed on a high-cholesterol diet for 6 or 9 weeks. Atherosclerotic plaque size and composition were assessed by immunohistochemistry. RESULTS: Plaque size in response to OSS was increased in ApoE(-/-)Cx37(-/-) mice compared to ApoE(-/-) animals. Most plaques contained high lipid and macrophage content and a low amount of collagen. In ApoE(-/-) mice, macrophages were more prominent in LLSS than OSS plaques. This difference was reversed in ApoE(-/-)Cx37(-/-) animals, with a predominance of macrophages in OSS plaques. The increase in macrophage content in ApoE(-/-)Cx37(-/-) OSS plaques was mainly due to increased accumulation of M1 and Mox macrophage subtypes. Cx37 expression in macrophages did not affect their proliferation or their polarization in vitro. CONCLUSION: Cx37 deletion increased the size of atherosclerotic lesions in OSS regions and abrogated the development of a stable plaque phenotype under OSS in ApoE(-/-) mice. Hence, local hemodynamic factors may modify the risk for adverse atherosclerotic disease outcomes associated to a polymorphism in the human Cx37 gene.

Functional role of a polymorphism in the Pannexin1 gene in collagen-induced platelet aggregation.

Pannexin1 (Panx1) forms ATP channels that play a critical role in the immune response by reinforcing purinergic signal amplification in the immune synapse. Platelets express Panx1 and given the importance of ATP release in platelets, we investigated Panx1 function in platelet aggregation and the potential impact of genetic polymorphisms on Panx1 channels. We show here that Panx1 forms ATP release channels in human platelets and that inhibiting Panx1 channel function with probenecid, mefloquine or specific (10)Panx1 peptides reduces collagen-induced platelet aggregation but not the response induced by arachidonic acid or ADP. These results were confirmed using Panx1-/- platelets. Natural variations have been described in the human Panx1 gene, which are predicted to induce non-conservative amino acid substitutions in its coding sequence. Healthy subjects homozygous for Panx1-400C, display enhanced platelet reactivity in response to collagen compared with those bearing the Panx1-400A allele. Conversely, the frequency of Panx1-400C homozygotes was increased among cardiovascular patients with hyper-reactive platelets compared with patients with hypo-reactive platelets. Exogenous expression of polymorphic Panx1 channels in a Panx-deficient cell line revealed increased basal and stimulated ATP release from cells transfected with Panx1-400C channels compared with Panx1-400A expressing transfectants. In conclusion, we demonstrate a specific role for Panx1 channels in the signalling pathway leading to collagen-induced platelet aggregation. Our study further identifies for the first time an association between a Panx1-400A>C genetic polymorphism and collagen-induced platelet reactivity. The Panx1-400C variant encodes for a gain-of-function channel that may adversely affect atherothrombosis by specifically enhancing collagen-induced ATP release and platelet aggregation.

A purse-string suture at the level of internal inguinal ring, taking only the peritoneum leaving the distal sac: is it enough for inguinal hernia in pediatric patients?

PURPOSE: Although laparoscopic surgery in children has expanded in recent years. Laparoscopic hernia repair in children is still debatable. We aimed to summarize and describe our results of laparoscopic inguinal hernia repair and techniques among children. METHODS: Between March 2011 and April 2013, 98 children (67 male, 31 female) underwent laparoscopic inguinal hernia repair at the department of surgery. The clinical outcomes were collected retrospectively. RESULTS: The mean follow-up period was 22.6 months. Twelve patients were ex-premature infants and a contralateral patent processus vaginalis (PPV) was present in 37 of the 91 unilateral inguinal hernia patients. There were two postoperative complications (transient hydrocele, umbilical port site infection). The mean operative time was 46 min. Recurrence, metachronous hernia and testicular atrophy were not observed during the follow-up period. CONCLUSIONS: Our preliminary experiences suggest that the laparoscopic purse-string suture of internal inguinal opening of hernia sac could be a safe, effective, and reliable alternative for management of pediatric inguinal hernia.

Titration of the gap junction protein Connexin43 reduces atherogenesis.

Ubiquitous reduction of the gap junction protein Connexin43 (Cx43) in mice provides beneficial effects on progression and composition of atherosclerotic lesions. Cx43 is expressed in multiple atheroma-associated cells but its function in each cell type is not known. To examine specifically the role of Cx43 in immune cells, we have lethally irradiated low-density lipoprotein receptor-deficient mice and reconstituted with Cx43+/+, Cx43+/- or Cx43-/- haematopoietic fetal liver cells. Progression of atherosclerosis was significantly lower in aortic roots of Cx43+/- chimeras compared with Cx43+/+ and Cx43-/- chimeras, and their plaques contained significantly less neutrophils. The relative proportion of circulating leukocytes was similar between the three groups. Interestingly, the chemoattraction of neutrophils, which did not express Cx43, was reduced in response to supernatant secreted by Cx43+/- macrophages in comparison with the ones of Cx43+/+ and Cx43-/- macrophages. Cx43+/- macrophages did not differ from Cx43+/+ and Cx43-/- macrophages in terms of M1/M2 polarisation but show modified gene expression for a variety chemokines and complement components. In conclusion, titration of Cx43 expression in bone marrow-derived macrophages reduces atherosclerotic plaque formation and chemoattraction of neutrophils to the lesions.

Cx26 regulates proliferation of repairing basal airway epithelial cells.

The recovery of an intact epithelium following injury is critical for restoration of lung homeostasis, a process that may be altered in cystic fibrosis (CF). In response to injury, progenitor cells in the undamaged areas migrate, proliferate and re-differentiate to regenerate an intact airway epithelium. The mechanisms regulating this regenerative response are, however, not well understood. In a model of circular wound injury of well-differentiated human airway epithelial cell (HAEC) cultures, we identified the gap junction protein Cx26 as an important regulator of cell proliferation. We report that induction of Cx26 in repairing HAECs is associated with cell proliferation. We also show that Cx26 is expressed in a population of CK14-positive basal-like cells. Cx26 silencing in immortalized cell lines using siRNA and in primary HAECs using lentiviral-transduced shRNA enhanced Ki67-labeling index and Ki67 mRNA, indicating that Cx26 acts a negative regulator of HAEC proliferation. Cx26 silencing also markedly decreased the transcription of KLF4 in immortalized HAECs. We further show that CF HAECs exhibited deregulated expression of KLF4, Ki67 and Cx26 as well enhanced rate of wound closure in the early response to injury. These results point to an altered repair process of CF HAECs characterized by rapid but desynchronized initiation of HAEC activation and proliferation.

miR-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo.

Cancer cell resistance to paclitaxel continues to be a major clinical problem. In this study, we utilized microRNA (miRNA) arrays to screen for differentially expressed miRNAs in paclitaxel-resistant cell lines established in vitro. We observed concordant upregulation of miR-135a in paclitaxel-resistant cell lines representing three human malignancies. Subsequently, the role of miRNA-135a was evaluated in an in vivo model of paclitaxel resistance. In this model, mice were inoculated subcutaneously with a non-small cell lung carcinoma cell line and treated with paclitaxel for a prolonged period. In paclitaxel-resistant cell lines, established either in vitro or in vivo, blockage of miR-135a sensitized resistant cell lines to paclitaxel-induced cell death. We further demonstrated a correlation between paclitaxel response and miR-135a expression in paclitaxel-resistant subclones that were established in vivo. The paclitaxel-resistant phenotype of these subclones was maintained upon retransplantation in new mice, as shown by decreased tumor response upon paclitaxel treatment compared with controls. Upregulation of miR-135a was associated with reduced expression of the adenomatous polyposis coli gene (APC). APC knockdown increased paclitaxel resistance in parental cell lines. Our results indicate that paclitaxel resistance is associated with upregulation of miR-135a, both in vitro and in vivo, and is in part determined by miR-135a-mediated downregulation of APC.

Packing technique for endovascular coil embolisation of peripheral arterial pseudo-aneurysms with preservation of the parent artery: safety, efficacy and outcomes.

OBJECTIVES: To evaluate the endovascular treatment of pseudo-aneurysms (PAs) with super-selective coil embolisation using the 3D packing technique. DESIGN: Retrospective study of consecutive patients in one academic centre. MATERIALS: From 2002 to 2009, 16 patients (mean age 51.6 years, range 24-82) underwent PA sac packing with coils. Four patients were asymptomatic, nine had PA rupture, and three had other symptoms. Lesion location was as follows: splenic artery (8), carotid artery (2), hepatic artery (2), superior mesenteric artery (1), cystic artery (1), uterine artery (1), and hypogastric artery (1). METHODS: The sac was packed with 0.018-inch controlled-detachable microcoils, preserving the parent artery. Magnetic resonance angiography was done within 6 months, at 12 months then yearly. RESULTS: Technical success rate was 100%. Complete definitive PA exclusion was achieved with a single procedure in 15 (93.8%) patients. One patient with a secondary bleeding arterio-digestive fistula underwent successful surgery. No major complications or late recanalisations occurred during follow-up (mean, 24.7 months; range 6-49). CONCLUSIONS: Coil PA embolisation by 3D sac packing is safe and effective and may induce less morbidity than complete parent vessel occlusion, stent placement, or open surgery. This procedure should be used whenever possible, as it preserves parent artery patency.

3-bromopyruvate: a new targeted antiglycolytic agent and a promise for cancer therapy.

The pyruvate analog, 3-bromopyruvate, is an alkylating agent and a potent inhibitor of glycolysis. This antiglycolytic property of 3-bromopyruvate has recently been exploited to target cancer cells, as most tumors depend on glycolysis for their energy requirements. The anticancer effect of 3-bromopyruvate is achieved by depleting intracellular energy (ATP) resulting in tumor cell death. In this review, we will discuss the principal mechanism of action and primary targets of 3-bromopyruvate, and report the impressive antitumor effects of 3-bromopyruvate in multiple animal tumor models. We describe that the primary mechanism of 3-bromopyruvate is via preferential alkylation of GAPDH and that 3-bromopyruvate mediated cell death is linked to generation of free radicals. Research in our laboratory also revealed that 3-bromopyruvate induces endoplasmic reticulum stress, inhibits global protein synthesis further contributing to cancer cell death. Therefore, these and other studies reveal the tremendous potential of 3-bromopyruvate as an anticancer agent.

Endothelial-specific deletion of connexin40 promotes atherosclerosis by increasing CD73-dependent leukocyte adhesion.

BACKGROUND: Endothelial dysfunction is the initiating event of atherosclerosis. The expression of connexin40 (Cx40), an endothelial gap junction protein, is decreased during atherogenesis. In the present report, we sought to determine whether Cx40 contributes to the development of the disease. METHODS AND RESULTS: Mice with ubiquitous deletion of Cx40 are hypertensive, a risk factor for atherosclerosis. Consequently, we generated atherosclerosis-susceptible mice with endothelial-specific deletion of Cx40 (Cx40del mice). Cx40del mice were indeed not hypertensive. The progression of atherosclerosis was increased in Cx40del mice after 5 and 10 weeks of a high-cholesterol diet, and spontaneous lesions were observed in the aortic sinuses of young mice without such a diet. These lesions showed monocyte infiltration into the intima, increased expression of vascular cell adhesion molecule-1, and decreased expression of the ecto-enzyme CD73 in the endothelium. The proinflammatory phenotype of Cx40del mice was confirmed in another model of induced leukocyte recruitment from the lung microcirculation. Endothelial CD73 is known to induce antiadhesion signaling via the production of adenosine. We found that reducing Cx40 expression in vitro with small interfering RNA or antisense decreased CD73 expression and activity and increased leukocyte adhesion to mouse endothelial cells. These effects were reversed by an adenosine receptor agonist. CONCLUSIONS: Cx40-mediated gap junctional communication contributes to a quiescent nonactivated endothelium by propagating adenosine-evoked antiinflammatory signals between endothelial cells. Alteration in this mechanism by targeting Cx40 promotes leukocyte adhesion to the endothelium, thus accelerating atherosclerosis.

X-ray reflectivity study on the structure and phase stability of mixed phospholipid multilayers.

Vertically oriented multilayers composed of two saturated phospholipids, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoserine (DPPS), were deposited on silicon. X-ray reflectivity was used to investigate the structures of the variously mixed phospholipid multilayers as a function of composition. Then, the phase stability was investigated at various annealing temperatures under humid conditions. The results indicated that the lipid spacing of the mixed phospholipid multilayers varied systematically as a function of the DPPC/DPPS ratio and that no macroscopic phase separation occurred during the annealing process under both dry and humid conditions.

Preparation of doxorubicin-containing chitosan microspheres for transcatheter arterial chemoembolization of hepatocellular carcinoma.

A new form of doxorubicin hydrochloride (DRH)-containing chitosan microspheres (CMs) was prepared by employing an expanding-loading-shrinking (E-L-S) process. One hundred mg of pre-formed CMs were soaked in absolute ethanol and then placed in reduced pressure (the expanding process). Ten mg of DRH (2 mg ml(-1)) were added into the expanded CMs (the loading process). Next the microspheres were freeze-dried (the shrinking process). As a result of this E-L-S process, 10% (w/w) DRH-containing CMs (DRH-CM) were made. During 7 days, 22.6% of the DRH was observed to be released on the in vitro drug release study. In addition, these new DRH-CMs could be used for transcatheter arterial chemoembolization (TACE) procedure in VX2 hepatic tumour models of rabbit and the anti-tumour effects of DRH-CMs were investigated. On the post-CT scan 7 days after the TACE, total infarctions of the VX2 tumour were observed in 5 rabbits among the 6 total rabbits.

An experimental model of ischemia in rabbit hindlimb.

This study was performed to establish an experimental model of ischemia for the investigation of new treatment modality of limb-threatening ischemia. We produced ischemia in the hindlimbs of 8 New Zealand white rabbits. Under general anesthesia, the left femoral artery was exposed, freed, and excised from distal external iliac artery to proximal popliteal and saphenous arteries. And then both hindlimbs were serially examined to assess the ischemia according to the time table until postoperative 6 weeks. We assessed clinical observation, blood pressure, radioisotopic perfusion scan, and angiography. Clinical ischemic changes of the operated feet were observed in 63%. The blood pressure of left calves was measurable on postoperative day 3 (p<0.05, vs preoperative day 2) and then gradually increased to reach a plateau in postoperative week 6. Radioisotopic arterial perfusion showed similar profiles as in blood pressure. Angiography of ischemic hindlimbs demonstrated a few collateral vessels arising from the internal iliac artery with the reconstitution of the posterior tibial artery in postoperative week 2. In postoperative week 6, collaterals remained the same in number. However, these became dilated and tortuous and showed reconstitution in distal hindleg. In conclusion, this is a reproducible, measurable, and economical animal model of hind limb ischemia.

Hepatocellular carcinoma: correlation between vascular endothelial growth factor level and degree of enhancement by multiphase contrast-enhanced computed tomography.

RATIONALE AND OBJECTIVES: To determine whether vascular endothelial growth factor (VEGF) is a histopathological factor influencing contrast enhancement of hepatocellular carcinoma (HCC) on computed tomography (CT). METHODS: Twenty-two nodular HCCs underwent multiphase helical CT and surgery. Tumor size, histological grading of differentiation, and type of hepatitis were evaluated. Tumor attenuation was graded as hyperattenuated, isoattenuated, and hypoattenuated. Immunohistochemical staining with anti-VEGF antibody was performed and scored as weak, intermediate, or strong. Spearman's rank correlation test was used. RESULTS: Tumors ranged from 1.0 to 12.0 cm (mean 5.1 cm). The degree of enhancement during the hepatic arterial phase was significantly correlated with VEGF expression. Size was negatively correlated with VEGF expression and the degree of enhancement, but histological grade and type of hepatitis were not correlated with VEGF expression, tumor size, or degree of enhancement. CONCLUSIONS: In HCC, VEGF expression is correlated with the degree of contrast enhancement during arterial-phase CT.

Cd40 ligand-deficient mice are protected against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.

BACKGROUND AND AIMS: The interactions between inflammatory cells and their mediators play important roles in many inflammatory processes, but their importance during acute experimental pancreatitis and pancreatitis-associated lung injury is unclear. To address the role of the interaction between CD40 and its ligand CD40L, molecules that mediate major immunoregulatory functions, pancreatitis was induced by administering supramaximal doses of cerulein in mice that do not express CD40L. METHODS: The severity of pancreatitis was measured by serum amylase activity, pancreatic edema, acinar cell necrosis, and pancreas myeloperoxidase activity (an indicator of neutrophil infiltration). Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. RESULTS: In pancreatic tissue from control mice and cerulein-treated mice, the expression of both CD40 and CD40L was detected. Immunohistochemical analysis performed in isolated acini from wild-type pancreata showed that both CD40 and CD40L were expressed on the acinar cell surface. Interestingly, pancreatitis and pancreatitis-associated lung injury were markedly decreased in mice deficient in CD40L compared with wild-types. CONCLUSIONS: These observations indicate that CD40L plays an important proinflammatory role in pancreatitis and pancreatitis-associated lung injury.

Correlation of VEGF with contrast enhancement on dual-phase dynamic helical CT in liver tumors: preliminary study.

The purpose of this preliminary study is to elucidate that vascular endothelial growth factor (VEGF) influences contrast enhancement of hepatic tumors on computed tomography (CT). Fourteen patients with hepatic tumors (11 hepatocellular carcinomas; 3 metastatic cancers) underwent a dual-phase dynamic helical CT or computed tomographic hepatic arteriography. The attenuation of each mass was determined as hyperattenuation, isoattenuation or hypoattenuation with respect to the adjacent nontumorous parenchyma. Gun-needle biopsy was done for each tumor, and paraffin sections were immunostained with anti- VEGF antibody by the avidin-biotin-peroxidase complex method. The pathologic grade was made by intensity (1 +, 2+, 3+) and area (+/-, 1 +, 2+). The tumor ranged 2.0-14.0 cm in size (mean, 5.8 cm). In arterial phase, the intensity was not correlated with the degree of enhancement (p=0.086). However, the correlation between the attenuation value of hepatic arterial phase and the area of positive tumor cells was statistically significant (p=0.002). VEGF may be the factor that enhances the hepatic mass with water-soluble iodinated contrast agent in CT.

Inhibition of endothelial wound repair by dominant negative connexin inhibitors.

Wounding of endothelial cells is associated with altered direct intercellular communication. To determine whether gap junctional communication participates to the wound repair process, we have compared connexin (Cx) expression, cell-to-cell coupling and kinetics of wound repair in monolayer cultures of PymT-transformed mouse endothelial cells (clone bEnd.3) and in bEnd.3 cells expressing different dominant negative Cx inhibitors. In parental bEnd.3 cells, mechanical wounding increased expression of Cx43 and decreased expression of Cx37 at the site of injury, whereas Cx40 expression was unaffected. These wound-induced changes in Cx expression were associated with functional changes in cell-to-cell coupling, as assessed with different fluorescent tracers. Stable transfection with cDNAs encoding for the chimeric connexin 3243H7 or the fusion protein Cx43-betaGal resulted in perturbed gap junctional communication between bEnd.3 cells under both basal and wounded conditions. The time required for complete repair of a defined wound within a confluent monolayer was increased by ~50% in cells expressing the dominant negative Cx inhibitors, whereas other cell properties, such as proliferation rate, migration of single cells, cyst formation and extracellular proteolytic activity, were unaltered. These findings demonstrate that proper Cx expression is required for coordinated migration during repair of an endothelial wound.