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PURPOSE: We introduce a novel technique for closed chamber iridodialysis repair. MATERIALS AND METHODS: We use a 2.8-mm paracentesis knife to penetrate into the anterior chamber and create interrupted incisions in the sclera. The wounds are 1.5 mm distant from the limbus, at consistent 2.8-mm intervals along the dialysis area. After injecting viscocohesive ophthalmic viscosurgical device through a side port to relieve the synechia and to push the iris toward the incisions, the iris is then grasped by Kelman forceps through the sclera, dragged carefully, and incarcerated. After adjusting the tension of the iris according to the pupil shape, the sclera and the incarcerated iris tissue were sutured together with 10-0 nylon. RESULTS: The technique was effective in six patients with traumatic iridodialysis. CONCLUSION: Our surgical technique repairs the iris, restores the shape of pupil, as well as avoids creating a large incision in the limbus in patients suffering from iridodialysis.

Epstein Barr virus (EBV) uses various strategies to manipulate host cytokine production in favor of the survival of infected B-cells. Microarray and cytokine protein array assays revealed that tissue inhibitor of metalloproteinase-1 (TIMP-1) was significantly up-regulated in EBV-infected primary B cells and maintained in abundance in EBV-immortalized lymphoblastoid cell lines (LCLs). TIMP-1 plays critical roles in extracellular matrix homeostasis and regulates signaling pathways. In this study, we demonstrated that the EBV-encoded immediate early lytic protein, Zta, upregulates mainly TIMP-1 expression by binding to the AP-1 site within the TIMP-1 promoter. Moreover, knockdown of TIMP-1 expression promoted cisplastin and cold shock-induced death of LCLs. This study provides a mechanistic link between EBV-induced TIMP-1 expression and its impact on LCL survival.

Whether markets are efficient or not has been broadly discussed in the empirical literature since the efficient markets hypothesis was proposed by Fama and others in the 1960s. Unfortunately, they did not come to a consistent conclusion. Besides, while these studies show whether a specific market is efficient or not, little has been done to explore the issues regarding the degree of market inefficiency. This paper attempts to resolve the puzzle of the inconsistent conclusions in the empirical literature by adopting a bottom-up approach which takes market participants’ interactions and coordination into consideration. By simulating an agent-based artificial stock market, this paper concludes with three main findings. First, agents’ survivability is mainly decided by risk preference, and not forecasting accuracy. Survivors may have diverse forecasting accuracy. Second, because market prices are not decided by agents based on accurate predictions, markets can not be efficient. What may exist is only the difference of the degree of inefficiency between markets. Third, the more relevant to survivability the forecasting accuracy in a market is, the less inefficient the market will be. Therefore, this paper suggests that it may be better to view the divergent empirical results regarding market efficiency as a fact that markets are inefficient to a variety of degrees.

Purpose.To evaluate the clinical outcomes in patients with central retinal vein occlusion (CRVO) treated with full-thickness retinochoroidal incisions and to compare whether there is difference in treatment response in ischemic and nonischemic CRVO.Methods.Retrospective study of patients of CRVO receiving full-thickness retinochoroidal incisions in Changhua Christian Hospital. Fluorescein angiography (FA), slit-lamp biomicroscopy, indirect funduscopy, best corrected visual acuity, and central macular thickness (CMT) measured by optical coherence tomography were performed pre- and postoperatively. Patients were divided into an ischemic and nonischemic group according to the findings of FA. Patients were followed up for at least 1 year.Results.Twenty-eight eyes (14 ischemic and 14 nonischemic CRVO) were included. Functional retinochoroidal venous anastomosis (RCVA) was achieved in 48 of the 65 retinochoroidal incisions (73.8%). Central macular thickness (CMT) and retinal hemorrhage decreased significantly after the surgery. Significant visual gain was observed postoperatively in the nonischemic group, but not in the ischemic group. Postoperative complications included vitreous hemorrhage (17.8%), neovascular glaucoma (7.1%), and preretinal fibrovasular membrane (10.7%), all of which were in the ischemic group.Conclusions.RCVA formation induced by retinochoroidal incisions could improve venous flow, and decrease CMT and retinal hemorrhage. However, only eyes with nonischemic CRVO showed visual improvement.

For maximum utilization of layout area using the vertical gate-all-around (VGAA) MOSFETs, this paper proposes a new S-shaped GAA (SGAA) MOSFET structure for 3D integration. The proposed approach improves the layout density per unit cell to extend Moore's Law without the need of aggressive technology scaling. By adjusting the dimensional parameters in the layout schematic, we can tune the device performance such as drive current easily, thus providing a circuit design flexibility for SoC application. Using the same effective channel width for comparison with others vertical GAA structures, the proposed one gives an advantage in better short-channel effects based on three-dimensional TCAD simulation. In addition, by interlacing SGAAs in a repeated unit cell configuration for high density design, just like multi-finger layout, the area density is increased by 3.3× as compared with the ring-shaped GAA MOSFET.

In recent years, semiconducting polymer dots (Pdots) have emerged as a novel class of extraordinarily bright fluorescent probes with burgeoning applications in bioimaging and sensing. While the desire for near-infrared (NIR)-emitting agents for in vivo biological applications increases drastically, the direct synthesis of semiconducting polymers that can form Pdots with ultrahigh fluorescence brightness is extremely lacking due to the severe aggregation-caused quenching of the NIR chromophores in Pdots. Here we describe the synthesis of dithienylbenzoselenadiazole (DBS)-based NIR-fluorescing Pdots with ultrahigh brightness and excellent photostability. More importantly, the fluorescence quantum yields of these Pdots could be effectively increased by the introduction of long alkyl chains into the thiophene rings of DBS to significantly inhibit the aggregation-caused emission quenching. Additionally, these new series of DBS-based Pdots can be excited by a commonly used 488 nm laser and show a fluorescence quantum yield as high as 36% with a Stokes shift larger than 200 nm. Single-particle analysis indicates that the per-particle brightness of the Pdots is at least 2 times higher than that of the commercial quantum dot (Qdot705) under identical laser excitation and acquisition conditions. We also functionalized the Pdots with carboxylic acid groups and then linked biomolecules to Pdot surfaces to demonstrate their capability for specific cellular labeling without any noticeable nonspecific binding. Our results suggest that these DBS-based NIR-fluorescing Pdots will be very practical in various biological imaging and analytical applications.

Semiconducting polymer dots (P-dots) recently have emerged as a new type of ultrabright fluorescent probe with promising applications in biological imaging and detection. With the increasing desire for near-infrared (NIR) fluorescing probes for in vivo biological measurements, the currently available NIR-emitting P-dots are very limited and the leaching of the encapsulated dyes/polymers has usually been a concern. To address this challenge, we first embedded the NIR dyes into the matrix of poly[(9,9-dioctylfluorene)-co-2,1,3-benzothiadiazole-co-4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole] (PF-BT-DBT) polymer and then enclosed the doped P-dots with polydiacetylenes (PDAs) to avoid potential leakage of the entrapped NIR dyes from the P-dot matrix. These PDA-enclosed NIR-emitting P-dots not only emitted much stronger NIR fluorescence than conventional organic molecules but also exhibited enhanced photostability over CdTe quantum dots, free NIR dyes, and gold nanoclusters. We next conjugated biomolecules onto the surface of the resulting P-dots and demonstrated their capability for specific cellular labeling without any noticeable nonspecific binding. To employ this new class of material as a facile sensing platform, an easy-to-prepare test paper, obtained by soaking the paper into the PDA-enclosed NIR-emitting P-dot solution, was used to sense external stimuli such as ions, temperature, or pH, depending on the surface functionalization of PDAs. We believe these PDA-coated NIR-fluorescing P-dots will be very useful in a variety of bioimaging and analytical applications.

A number of theoretical studies have explained the existence of arbitrage opportunity with so called ¡§noise traders¡¨ (e.g., De Long et al., 1990; Shleifer and Vishny, 1997; Abreu and Brunnermeier, 2002). In fact, noise traders can create the arbitrage opportunity because they are quite influential in these papers. However, by taking endowments into consideration, the large numbers of noise traders in real markets are not necessarily sufficiently influential. Moreover, theoretical papers assume that investors, apart from the noise traders, have perfect foresight, which is also far away from the situation in real financial markets. By relaxing the strong assumptions of a representative agent and perfect foresight in economics, this paper unravels the puzzle of the existence of arbitrage opportunity based on an agent-based artificial stock market.

Epstein-Barr virus (EBV) alters the regulation and expression of a variety of cytokines in its host cells to modulate host immune surveillance and facilitate viral persistence. Using cytokine antibody arrays, we found that, in addition to the cytokines reported previously, two chemotactic cytokines, CCL3 and CCL4, were induced in EBV-infected B cells and were expressed at high levels in all EBV-immortalized lymphoblastoid cell lines (LCLs). Furthermore, EBV latent membrane protein 1 (LMP1)-mediated Jun N-terminal protein kinase activation was responsible for upregulation of CCL3 and CCL4. Inhibition of CCL3 and CCL4 in LCLs using a short hairpin RNA approach or by neutralizing antibodies suppressed cell proliferation and caused apoptosis, indicating that autocrine CCL3 and CCL4 are required for LCL survival and growth. Importantly, significant amounts of CCL3 were detected in EBV-positive plasma from immunocompromised patients, suggesting that EBV modulates this chemokine in vivo . This study reveals the regulatory mechanism and a novel function of CCL3 and CCL4 in EBV-infected B cells. CCL3 might be useful as a therapeutic target in EBV-associated lymphoproliferative diseases and malignancies.

Impaired counterregulation during hypoglycemia in type 1 diabetes (T1D) is partly attributable to inadequate glucagon secretion. Intra-islet somatostatin (SST) suppression of hypoglycemia-stimulated α-cell glucagon release plays an important role. We hypothesized that hypoglycemia can be prevented in autoimmune T1D by SST receptor type 2 (SSTR2) antagonism of α-cells, which relieve SSTR2 inhibition, thereby increasing glucagon secretion. Diabetic biobreeding diabetes-prone (BBDP) rats mimic insulin-dependent human autoimmune T1D, whereas nondiabetic BBDP rats mimic prediabetes. Diabetic and nondiabetic rats underwent a 3-h infusion of vehicle compared with SSTR2 antagonist (SSTR2a) during insulin-induced hypoglycemia clamped at 3 ± 0.5 mmol/L. Diabetic rats treated with SSTR2a needed little or no glucose infusion compared with untreated rats. We attribute this effect to SSTR2a restoration of the attenuated glucagon response. Direct effects of SSTR2a on α-cells was assessed by resecting the pancreas, which was cut into fine slices and subjected to perifusion to monitor glucagon release. SSTR2a treatment enhanced low-glucose–stimulated glucagon and corticosterone secretion to normal levels in diabetic rats. SSTR2a had similar effects in vivo in nondiabetic rats and promoted glucagon secretion from nondiabetic rat and human pancreas slices. We conclude that SST contributes to impaired glucagon responsiveness to hypoglycemia in autoimmune T1D. SSTR2a treatment can fully restore hypoglycemia-stimulated glucagon release sufficient to attain normoglycemia in both diabetic and prediabetic stages.

Early-stage type 1 diabetes (T1D) exhibits hyperglucagonemia by undefined cellular mechanisms. Here we characterized α-cell voltage-gated ion channels in a streptozotocin (STZ)-induced diabetes model that lead to increased glucagon secretion mimicking T1D. GYY mice expressing enhanced yellow fluorescence protein in α cells were used to identify α cells within pancreas slices. Mice treated with low-dose STZ exhibited hyperglucagonemia, hyperglycemia, and glucose intolerance, with 71% reduction of β-cell mass. Although α-cell mass of STZ-treated mice remained unchanged, total pancreatic glucagon content was elevated, coinciding with increase in size of glucagon granules. Pancreas tissue slices enabled in situ examination of α-cell electrophysiology. α cells of STZ-treated mice exhibited the following: 1) increased exocytosis (serial depolarization-induced capacitance), 2) enhanced voltage-gated Na+ current density, 3) reduced voltage-gated K+ current density, and 4) increased action potential (AP) amplitude and firing frequency. Hyperglucagonemia in STZ-induced diabetes is thus likely due to increased glucagon content arising from enlarged glucagon granules and increased AP firing frequency and amplitude coinciding with enhanced Na+ and reduced K+ currents. These alterations may prime α cells in STZ-treated mice for more glucagon release per cell in response to low glucose stimulation. Thus, our study provides the first insight that STZ treatment sensitizes release mechanisms of α cells.

Hepatocellular carcinoma (HCC) relies on angiogenesis for growth and metastasis. Leukocyte cell-derived chemotaxin 2 (LECT2) is a cytokine and preferentially expressed in the liver. Previous studies have found that LECT2 targets to both immune and tumor cells to suppress HCC development and vascular invasion. Although LECT2 did not affect HCC cells growth in vitro, it still suppressed HCC xenografts growth in immune-deficient mice, suggesting other cells such as stroma cells may also be targeted by LECT2. Here, we sought to determine the role of LECT2 in tumor angiogenesis in HCC patients. We found that LECT2 expression inhibited tumor growth via angiogenesis in the HCC xenograft model. Specifically, we demonstrated that recombinant human LECT2 protein selectively suppressed vascular endothelial growth factor (VEGF)165-induced endothelial cell proliferation, migration, and tube formation in vitro and in vivo. Mechanistically, LECT2 reduced VEGF receptor 2 tyrosine phosphorylation and its downstream extracellular signal-regulated kinase and AKT phosphorylation. Furthermore, LECT2 gene expression correlated negatively with angiogenesis in HCC patients. Taken together, our findings demonstrate that LECT2 inhibits VEGF165-induced HCC angiogenesis through directly binding to VEGFR2 and has broad applications in treating VEGF-mediated solid tumors.

This paper proposes an area efficient gate-all-around ring (GAAR) MOSFET structure for vertical integration, which in essence is an arc-shaped double-gate FinFET and gains benefits of the superior gate control in GAA MOSFETs and feasible manufacturability. Such new structure offers another advantage of tunable performance by changing the size of the ring, giving a simple circuit design flexibility for various performance need for SoC application, especially for vertical transistors with the same gate length. It is shown that a 40% reduction in area is achieved using the vertical GAAR, as compared with conventional multi-fin MOSFETs.

A cDNA encoding mature human tyrosinase was cloned into pET-23a(+) and transformed into E. coli BL21(DE3). Three major recombinant proteins, mature human tyrosinase (RHT₂₀₋₅₃₁), N-terminal truncated human tyrosinase (RHT₁₆₈₋₅₃₁), and β-lactamase, were overexpressed as inclusion bodies in E. coli after 12 h of induction with 1.0 mM isopropyl-β-D-thiogalactopyranoside at 37 °C. After sonication and centrifugation, the inclusion body was harvested, solubilized, dialyzed, and refolded into the active form with monophenolase and diphenolase activities. It was purified to homogeneity by DEAE-Sepharose FF and Sephadex G-75. The molecular mass and N-terminal sequence were 57.0 kDa and GHFPRAC, respectively, and corresponded to those of mature human tyrosinase. The RHT was active in a broad range of temperature and pH, and with optimum activity at 70 °C and pH 8.5.

In this study, we aimed to examine the electrophysio- logical properties of β-cells in Kir6.2-/- mice using fresh pancreatic tissue slice preparation. This prepa-ration is advantageous since it preserves socio-cellular context of the β-cells. Using this novel approach we revisited basic morphology and used whole-cell patch-clamp to study electrical excitability as well as to assess the modulation of the late steps of the exocy-totic activity of β-cells by cytosolic [Ca2+] changes in control and Kir6.2-/- mice. We found that young Kir6.2-/- mice (2 - 4 weeks old) were hypoglycaemic while aged Kir6.2-/- mice (5 - 60 weeks old) were normo- or even hyper- glycaemic. Membrane ca-pacitance measurements show- ed more efficient Ca2+-secretion coupling in young Kir6.2-/- mice, but this coupling is significantly reduced in older Kir6.2-/- mice. We have found increased exo- cytotic efficacy induced by repetitive trains of depo- larization pulses which may result from higher cyto- solic [Ca2+] due to hyperexcitability in Kir6.2-/- mice. This condition in turn resulted in the reduced β-cell number and func-tion in the following weeks. Detailed assessment of the efficacy of Ca2+ dependent exocyto- sis in β-cell from Kir6.2-/- mice may contribute to our understanding of the pathophysiology of persistent hyperinsulinemia hypoglycemia of infancy (PHHI) and suggest potential alternative therapeutic approaches for PHHI patients.

Critical investigation into α-cell biology in health and diabetes has been sparse and at times inconsistent because of the technical difficulties with employing conventional strategies of isolated islets and dispersed single cells. An acute pancreas slice preparation was developed to overcome the enzymatic and mechanical perturbations inherent in conventional islet cell isolation procedures. This preparation preserves intra-islet cellular communication and islet architecture in their in situ native state. α-Cells within tissue slices were directly assessed by patch pipette and electrophysiologically characterized. The identity of the patched cells was confirmed by biocytin dye labelling and immunocytochemistry. α-Cells in mouse pancreas slices exhibited well-described features of I(Na) (excitable at physiological membrane potential), I(KATP), small cell size, low resting membrane conductance, and inducible low and high voltage-activated I(Ca), the latter correlating with exocytosis determined by capacitance measurements. In contrast to previous reports, our large unbiased sampling of α-cells revealed a wide range distribution of all of these parameters, including the amount of K(ATP) conductance, Na+ and Ca2+ current amplitudes, and capacitance changes induced by a train of depolarization pulses. The proposed pancreas slice preparation in combination with standard patch-clamping technique allowed large sampling and rapid assessment of α-cells, which revealed a wide distribution in α-cell ion channel properties. This specific feature explains the apparent inconsistency of previous reports on these α-cell ion channel properties. Our innovative approach will enable future studies into elucidating islet α-cell dysregulation occurring during diabetes.

The relevance of risk preference and forecasting accuracy to the survival of investors is an issue that has recently attracted a number of theoretical studies. By using agent-based computational modeling, this paper extends the existing studies to an economy where adaptive behaviors are autonomous and complex heterogeneous. Specifically, a computational multi-asset artificial stock market corresponding to Blume and Easley [Blume, L., Easley, D., 1992. Evolution and market behavior. Journal of Economic Theory 58, 9–40] and Sandroni [Sandroni, A., 2000. Do markets favor agents able to make accurate predictions? Econometrica 68, 1303–1341] is constructed and studied. Through simulation, we present results that contradict the market selection hypothesis.

As a follow-up to the work of Chen and Huang [S.-H. Chen, Y.-C. Huang, Risk preference, forecasting accuracy and survival dynamics: simulations based on a multi-asset agent-based artificial stock market, Working Paper Series 2004-1, AI-ECON Research Center, National Chengchi University, 2004; S.-H. Chen, Y.-C. Huang, Risk preference and survival dynamics, in: T. Terano, H. Kita, T. Kaneda, K. Arai, H. Deghchi (Eds.), Agent-Based Simulation: From Modeling Methodologies to Real-World Applications, Springer Series on Agent-Based Social Systems, vol. 1, 2005, pp. 135-143], this paper continues to explore the relationship between wealth share dynamics and risk preferences in the context of an agent-based multi-asset artificial stock market. We simulate a multi-asset agent-based artificial stock market composed of heterogeneous agents with different degrees of relative risk aversion. As before, we find that the difference in risk aversion and the resultant saving behavior are the primary forces in determining the survivability of agents. In addition to the stability of the saving behavior, the level of the saving rate also plays a crucial role. The agents with stable saving behavior, e.g., the log-utility agents, may still become extinct because of their low saving rates, whereas the agents with unstable saving behavior may survive because of their high saving rates, implied by their highly risk-averse preferences.

Purpose – The purpose of this paper is to propose a model that captures the fuzzy events is proposed to find the optimal periods of warranty policies. The model considers repair and replacement actions in the warranty period.Design/methodology/approach – The study transforms the reliability of a traditional set to a fuzzy reliability set that models a problem. The optimality of the model is explored with classical optimal theory. Also, a numerical example is presented to describe how to find an optimal warranty policy.Findings – The study proves that the optimality of a warranty model can be used to find the optimal warranty policy in a fuzzy environment.Originality/value – The model is useful for firms in deciding what the maintenance strategy and warranty period should be in a fuzzy environment.

The myeloid sarcoma is an extramedullary finding of acute myeloid leukemia (AML), and orbital leukemic tumors occur most commonly during the first decade of life. To our knowledge, we report the youngest patient with bilateral proptosis of both eyes as an initial manifestation of AML. This case highlights the need for peripheral blood smear and neuro-image work-up for acute proptosis in infancy. AML should be considered in the differential diagnosis of an orbital mass, even in the absence of typical leukemic symptoms.

Recently, semiconducting polymer dots (Pdots) have become a novel type of ultrabright fluorescent probes which hold great promise in biological imaging and analytical detection. Here we developed a visual sensor based on Pdots for Pb(2+) detection. We first embedded near-infrared (NIR) dyes into the matrix of poly[(9,9-dioctylfluorene)-co-2,1,3-benzothiadiazole-co-4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole] (PFBT-DBT) polymer and then capped the Pdots with polydiacetylenes (PDAs), in which parts of the PDAs were prefunctionalized with 15-crown-5 moieties to form Pdots. The high selectivity of these Pdots for lead ions is attributed to the formation of 2:1 15-crown-5-Pb(2+)-carboxylate sandwich complex on the Pdot surface. After Pb(2+) chelation, the conjugation system of the PDA was perturbed and strained, causing a chromatic change of the PDA from blue to red. At the same time, the encapsulated NIR dyes were liable to leach out that resulted in an emission variation of the Pdots. Accordingly, lead ions can be recognized by either color change or emission variation of the Pdots. We also loaded these nanoprobes into live HeLa cells through endocytosis, and then monitored changes in Pb(2+) levels within cells, demonstrating their utility for use in cellular and bioimaging applications. In addition, we fabricated easy-to-prepare test strips impregnated with Pdot-poly(vinyl alcohol) films to identify Pb(2+) in real samples, which proved their applicability for in situ on-site detection. Our results suggest that this Pdot-based visual sensor shows promising potential for advanced environmental and biological applications.

Objective: Pancreatic beta-cells express three Munc18 isoforms. Much is known about the roles of Munc18a (pre-docked secretory granules-SGs) and Munc18b (newcomer SGs and SG–SG fusion) in insulin exocytosis. Although shown to influence glucose-stimulated insulin secretion (GSIS) in rodents the precise role of Munc18c in insulin SG exocytosis has not been elucidated. We here examined the role of Munc18c in human pancreatic beta-cells. Methods: Munc18c-shRNA/RFP lenti-virus (versus control virus) was used to knock down the expression level of Munc18c in human islets or single beta-cells. Insulin secretion and granule exocytosis were measured by performing islets perifusion, single-cell patch clamp capacitance measurements and total internal reflection fluorescence microscopy (TIRFM). Results: Munc18c is most abundant in the cytosol of human beta-cells. Endogenous function of Munc18c was assessed by knocking down (KD) its islet expression by 70% employing lenti-shRNA virus. Munc18c-KD caused reduction in cognate syntaxin-4 islet expression but not in other exocytotic proteins, resulting in the reduction in GSIS in first- (by 42%) and second phases (by 35%). Single cell analyses of RFP-tagged Munc18c-KD beta-cells by patch clamp capacitance measurements showed inhibition in both readily-releasable pool (by 52%) and mobilization from the reserve pool (by 57%). TIRFM to assess single SG behavior showed that Munc18c-KD inhibition of first phase GSIS was attributed to reduction in exocytosis of pre-docked and newcomer SGs, and second phase inhibition attributed entirely to reduction in newcomer SG fusion (SGs that undergo minimal residence or docking time at the plasma membrane before fusion). Conclusion: Munc18c is involved in the distinct molecular machineries that affect exocytosis of both predocked and newcomer SG pools that underlie Munc18c's role in first and second phases of GSIS, respectively.

Purpose The objective of this study is to evaluate the myopic shift in sulcus suture-fixated posterior chamber intraocular lenses (PC IOLs). Methods It was a retrospective study of patients diagnosed with lens subluxation or aphakia who received sulcus suture-fixated PC IOLs from 2004 to 2010. Preoperative visual acuity; axial length; predicted IOL power by the SRK-T, Hoffer-Q, and Holladay-1 formulas; predicted refraction; postoperative visual acuity; and postoperative refraction were recorded. Differences between postoperative refraction and predicted refraction for an in-the-bag lens were calculated for each patient. Results Twenty eyes from 16 patients with sulcus suture-fixated PC IOLs were included in the study. Another 18 eyes from 18 patients with in-the-bag fixation of IOL were assigned to the control group. In a study group, the difference between postoperative spherical equivalent and predicted refraction was −1.66 ± 0.97 D. The simple linear regression suggests that the SRK-T formula provides a better calculation of IOL power than other formulas for sulcus suture fixation of PC IOL using our technique. A comparison of postoperative refraction shifts between the study and the control groups showed that the myopic shift was statistically significant in the study group (p Conclusion Sulcus suture-fixation of a PC IOL induces, on average, a 1.66 D myopic shift, which is equivalent to an IOL power of around 2 D. In order to prevent a postoperative hyperopia refraction, we suggest that IOL power should be reduced to 1–1.5 D for performing sulcus fixation using our technique.

Of the four exocytotic syntaxins (Syns), much is now known about the role of Syn-1A (pre-docked secretory granules [SGs]) and Syn-3 (newcomer SGs) in insulin exocytosis. Some work was reported on Syn-4's role in biphasic glucose-stimulated insulin secretion (GSIS), but its precise role in insulin SG exocytosis remains unclear. In this paper we examine this role in human beta cells.Endogenous function of Syn-4 in human islets was assessed by knocking down its expression with lentiviral single hairpin RNA (lenti-shRNA)-RFP. Biphasic GSIS was determined by islet perifusion assay. Single-cell analysis of exocytosis of red fluorescent protein (RFP)-positive beta cells (exhibiting near-total depletion of Syn-4) was by patch clamp capacitance measurements (Cm) and total internal reflection fluorescence microscopy (TIRFM), the latter to further assess single SG behaviour. Co-immunoprecipitations were conducted on INS-1 cells to assess exocytotic complexes.Syn-4 knockdown (KD) of 77% in human islets caused a concomitant reduction in cognate Munc18c expression (46%) without affecting expression of other exocytotic proteins; this resulted in reduction of GSIS in the first phase (by 42%) and the second phase (by 40%). Cm of RFP-tagged Syn-4-KD beta cells showed severe inhibition in the readily releasable pool (by 71%) and mobilisation from reserve pools (by 63%). TIRFM showed that Syn-4-KD-induced inhibition of first-phase GSIS was attributed to reduction in exocytosis of both pre-docked and newcomer SGs (which undergo minimal residence or docking time at the plasma membrane before fusion). Second-phase inhibition was attributed to reduction in newcomer SGs. Stx-4 co-immunoprecipitated Munc18c, VAMP2 and VAMP8, suggesting that these exocytotic complexes may be involved in exocytosis of pre-docked and newcomer SGs.Syn-4 is involved in distinct molecular machineries that influence exocytosis of both pre-docked and newcomer SGs in a manner functionally redundant to Syn-1A and Syn-3, respectively; this underlies Syn-4's role in mediating portions of first-phase and second-phase GSIS.

DNA methylation is a complex event in epigenetic studies because of both the large CpG islands present upstream of the promoter region and the different distribution of DNA methylation despite similar methylation levels. For this reason, we proposed a fast, cost-effective method for the screening of DNA methylation based on SSCP and CE-LIF. In this study, the PCR products that were amplified from bisulfite-treated genomic DNA were denatured at 94°C, followed by immediate chilling in ice water to form the ssDNA. The ssDNA were separated by 1.5% poly(ethylene oxide) (Mavg 8 000 000 Da) in the presence of EOF according to the different conformations represented by their unique methylation states. This result demonstrated that four hepatocellular carcinoma cell lines represented a different heterogeneity of DNA methylation and could be distinguished by SSCP-CE. The results obtained from SSCP-CE also corresponded with those obtained from combined bisulfide restriction analysis and methylation-sensitive high-resolution melting analysis. Therefore, the proposed SSCP-CE method may potentially be used for rapid screening for determination of the heterogeneity of DNA methylation in further epigenetic studies and clinical diagnosis.

Ischemic stroke contributes up to 80% of total stroke incidence and is one of the leading causes of death and disability worldwide1,2. Noteworthily, the inflammatory responses triggered after ischemic stroke often amplify and exacerbate the ischemic lesion2. Insufficient blood supply to brain cells initiates the pathophysiology of ischemic stroke and results in a densely ischemic core surrounded by a poorly perfused region termed ischemic penumbra. Cells within the ischemic area become deprived of oxygen, glucose, and other nutrients. Since oxygen and glucose are critical fuels for brain cell survival, lack of these factors leads to dysfunction of neurons, glial cells, endothelial cells, and pericytes. Neuronal microenvironments are no longer tightly maintained and disruption of the blood brain barrier (BBB) occurs. Blood borne immune cells start to infiltrate through the disrupted vessel walls into the ischemic area and release inflammatory mediators, which exaggerate brain edema and promote cell death in the penumbra to result in secondary infarct lesion1,3. Accordingly, ischemic stoke patients who arrived to the hospital within a short time window (3–4.5 h1,2,4) after stroke incidence are commonly treated with the thrombolytic agent, recombinant tissue plasminogen activator (tPA, commonly called “clot buster”), in an attempt to restore perfusion and minimize brain damage1,2. For patients who have missed the short time frame, there is no safe and efficacious treatment that is currently available3. This is because the thrombus in the occluded artery has become too firm for tPA to dissolve. Moreover, the BBB disruption is likely to occur at this point, which would allow tPA to gain excess into the extravascular compartment. tPA residing in the extravascular compartment is associated with higher risk of intracranial hemorrhage and neurotoxicity5. Therefore, the beneficial effect of tPA is greatly compromised in patients with prolonged and untreated ischemic stroke. To develop effective treatments for these patients, it is essential to understand the complex and incompletely defined post ischemic inflammatory response mechanisms. This article highlights a recent work reported by Hu and colleagues6, which sheds new light into the future management of post-ischemic stroke inflammation.

Investigation of α-cells has long been constrained by their scarce population and localization at the islet mantle which exposes α-cells to injury by conventional islet isolation and dispersion to single cells that employ damaging enzymatic and mechanical means. To surmount these limitations, we recently reported employing the pancreas slice preparation which enables highly efficient acute in situ electrophysiological (patch clamp) examination of α-cells within its unperturbed native social environment with preserved paracrine regulation. In this review, we compare the electrophysiological properties of α-cells in these three preparations, and discuss the current view of glucose regulation of α-cells. We discuss current genetic mouse models that flurophore-tagged α-cells (GYY) and β-cells (MIP-GFP) which can reliably identify islet cells to facilitate their study. Combining these strategies should enable future studies directed at the precise assessment of the perturbation in intrinsic and paracrine regulation of α-cells contributing to abnormal glucose homeostasis in diabetes.

Critical investigation into α-cell biology in health and diabetes has been sparse and at times inconsistent because of the technical difficulties with employing conventional strategies of isolated islets and dispersed single cells. An acute pancreas slice preparation was developed to overcome the enzymatic and mechanical perturbations inherent in conventional islet cell isolation procedures. This preparation preserves intra-islet cellular communication and islet architecture in their in situ native state. α-Cells within tissue slices were directly assessed by patch pipette and electrophysiologically characterized. The identity of the patched cells was confirmed by biocytin dye labelling and immunocytochemistry. α-Cells in mouse pancreas slices exhibited well-described features of I(Na) (excitable at physiological membrane potential), I(KATP), small cell size, low resting membrane conductance, and inducible low and high voltage-activated I(Ca), the latter correlating with exocytosis determined by capacitance measurements. In contrast to previous reports, our large unbiased sampling of α-cells revealed a wide range distribution of all of these parameters, including the amount of K(ATP) conductance, Na+ and Ca2+ current amplitudes, and capacitance changes induced by a train of depolarization pulses. The proposed pancreas slice preparation in combination with standard patch-clamping technique allowed large sampling and rapid assessment of α-cells, which revealed a wide distribution in α-cell ion channel properties. This specific feature explains the apparent inconsistency of previous reports on these α-cell ion channel properties. Our innovative approach will enable future studies into elucidating islet α-cell dysregulation occurring during diabetes.

With the rapid development of broadband networks and multimedia technologies, P2P video-on-demand service is increasingly gaining popularity over the past few years. However, little work has been done on an important design issue for P2P video-on-demand systems, i.e., determining the maximal service capacity of a system. In this paper, we first propose an optimal rate allocation scheme to maximize the service capacity of a P2P video-on-demand system. The proposed rate allocation scheme determines the parent/child relationship among peers and the link rates between peers. Then we develop an admission control policy based on the proposed rate allocation scheme. Our simulation results showed that the proposed scheme demonstrates high efficiency compared to other rate allocation schemes.

Cyclic AMP is a fundamentally important second messenger for numerous peptide hormones and neurotransmitters that control gene expression, cell proliferation, and metabolic homeostasis. Here we show that cAMP works with the POU homeodomain protein Oct-1 to regulate gene expression in pancreatic and intestinal endocrine cells. This ubiquitously expressed transcription factor is known as a stress sensor. We found that it also functions as a repressor of Cdx-2, a proglucagon gene activator. Through a mechanism that involves the activation of exchange protein activated by cyclic AMP, elevation of cAMP leads to enhanced phosphorylation and nuclear exclusion of Oct-1 and reduced interactions between Oct-1 or nuclear co-repressors and the Cdx-2 gene promoter, detected by chromatin immunoprecipitation. In rat primary pancreatic islet cells, cAMP elevation also reduces nuclear Oct-1 content, which causes increased proglucagon and proinsulin mRNA expression. Our study therefore identifies a novel mechanism by which cAMP regulates hormone-gene expression and suggests that ubiquitously expressed Oct-1 may play a role in metabolic homeostasis by functioning as a sensor for cAMP.

Synaptosomal protein of 25 kDa (SNAP-25) is important for Ca2+-dependent fusion of large dense core vesicles (LDCVs) in insulin-secreting cells. Exocytosis is further enhanced by cAMP-increasing agents such as glucagon-like peptide-1 (GLP-1), and this augmentation includes interaction with both PKA and cAMP-GEFII. To investigate the coupling between SNAP-25- and cAMP-dependent stimulation of insulin exocytosis, we have used capacitance measurements, protein-binding assays, and Western blot analysis. In insulin-secreting INS-1 cells overexpressing wild-type SNAP-25 (SNAP-25WT), rapid exocytosis was stimulated more than threefold by cAMP, similar to the situation in nontransfected cells. However, cAMP failed to potentiate rapid exocytosis in INS-1 cells overexpressing a truncated form of SNAP-25 (SNAP-251-197) or Botulinum neurotoxin A (BoNT/A). Close dissection of the exocytotic response revealed that the inability of cAMP to stimulate exocytosis in the presence of a truncated SNAP-25 was confined to the release of primed LDCVs within the readily releasable pool, especially from the immediately releasable pool, whereas cAMP enhanced mobilization of granules from the reserve pool in both SNAP-251-197( P < 0.01) and SNAP-25WT( P < 0.05) cells. This was supported by hormone release measurements. Augmentation of the immediately releasable pool by cAMP has been suggested to act through the cAMP-GEFII-dependent, PKA-independent pathway. Indeed, we were able to verify an interaction between SNAP-25 with both cAMP-GEFII and RIM2, two proteins involved in the PKA-independent pathway. Thus we hypothesize that SNAP-25 is a necessary partner in the complex mediating cAMP-enhanced rapid exocytosis in insulin-secreting cells.

This paper demonstrates the implementation of a responsive window which consists of an LCD-TV display and an ultrasonic location system. The window is perceptive because the main controller detects the location of the front observer by an ultrasonic system. The controller also manipulates the remote-end IP-camera to give a proper view which is corresponding to the location of the observer. The designs of both the ultrasonic system and the IP-camera control are described in this paper. Based on the ultrasonic location system, the observer in front of the responsive window needs not to wear anything. The test results show that the observer can manipulate the remote-end IP-camera simply by moving himself in front of the window. It is then verified that the perceptive window is able to be applied in the responsive environments.

There is a need for standard TIM characterization technique for notebook specific applications. The current standard method, ASTM D5470 tester neglects the usage conditions encountered in mobile specific applications. In addition, characterizing "Beginning of Life" performance of TIMs is not sufficient as performance can degrade with usage. This paper emphasizes the importance of considering TIM degradation in mobile applications. Varior TIM characterization approaches prevalent in industry are discussed in this paper. There is also wide disparity in testing methodologies used across industry to evaluate its performance maps with usage. A set of characterization techniques for better TIM evaluation practices are suggested.

There is a need for standard TIM characterization technique for notebook specific applications. The current standard method, ASTM D5470 tester neglects the usage conditions encountered in mobile specific applications. In addition, characterizing "Beginning of Life" performance of TIMs is not sufficient as performance can degrade with usage. This paper emphasizes the importance of considering TIM degradation in mobile applications. Various TIM characterization approaches prevalent in industry are discussed in this paper. There is also wide disparity in testing methodologies used across industry to evaluate its performance maps with usage. A set of characterization techniques for better TIM evaluation practices are suggested.

Closure of pancreatic beta-cell ATP-sensitive potassium (K(ATP)) channels links glucose metabolism to electrical activity and insulin secretion. It is now known that saturated, but not polyunsaturated, long-chain acyl-coenyzme A esters (acyl-CoAs) can potently activate K(ATP) channels when superfused directly across excised membrane patches, suggesting a plausible mechanism to account for reduced beta-cell excitability and insulin secretion observed in obesity and type 2 diabetes. However, reduced beta-cell excitability due to elevation of endogenous saturated acyl-CoAs has not been confirmed in intact pancreatic beta-cells. To test this notion directly, endogenous acyl-CoA levels were elevated within primary mouse beta-cells using virally delivered overexpression of long-chain acyl-CoA synthetase-1 (AdACSL-1), and the effects on beta-cell K(ATP) channel activity and cell excitability was assessed using the perforated whole-cell and cell-attached patch-clamp technique. Data indicated a significant increase in K(ATP) channel activity in AdACSL-1-infected beta-cells cultured in medium supplemented with palmitate/oleate but not with the polyunsaturated fat linoleate. No changes in the ATP/ADP ratio were observed in any of the groups. Furthermore, AdACSL-1-infected beta-cells (with palmitate/oleate) showed a significant decrease in electrical responsiveness to glucose and tolbutamide and a hyperpolarized resting membrane potential at 5 mm glucose. These results suggest a direct link between intracellular fatty ester accumulation and K(ATP) channel activation, which may contribute to beta-cell dysfunction in type 2 diabetes.

Synaptosome-associated protein of 25 kd (SNAP-25) regulates pancreatic islet beta-cell-delayed rectifier K channels (Kv2.1) in addition to insulin exocytosis. Botulinum neurotoxin A (BoNT/A) and E (BoNT/E) cleavage and presumed deletion of SNAP-25 have been used to examine SNAP-25 function. We hypothesized that proteolytic products of SNAP-25 (206 amino acids) resulting from BoNT/A and BoNT/E cleavage, SNAP-25(1-197) and SNAP-25(1-180), have independent actions on beta-cell Kv gating.We examined by confocal microscopy and immunoblotting BoNT/A and BoNT/E cleavage of SNAP-25 to these N-terminal fragments, and the consequent effects of these BoNTs and SNAP-25 fragments on Kv currents in rat beta cells and MIN6 cells by patch clamp electrophysiology.Confocal microscopy and immunoblotting showed that MIN6 cells transfected with BoNT/A or BoNT/E generated SNAP-25(1-197) and SNAP-25(1-180) fragments that were retained in the cytosol. Both BoNTs caused increased rate of channel activation and slowed channel inactivation, mimicked by these SNAP-25 fragments, but not full-length SNAP-25. These SNAP-25 fragments potentiated tetraethylammonium block of beta-cell Kv currents.BoNT/A or BoNT/E treatment of beta cells generates N-terminal SNAP-25 fragments that are retained in beta cells to directly influence Kv channel gating in a manner distinct from full-length SNAP-25, contributing to overall actions of these BoNTs on insulin secretion.

As a follow-up to the work of [4] and [5], this paper continues to explore the relationship between wealth share dynamics and risk preferences in the context of an agent-based multi-asset artificial stock market. We simulate a multiasset agent-based artificial stock market composed of heterogeneous agents with different degrees of relative risk aversion (RRA). A wide range of RRA coefficients has been found in the literature, and so far no unanimous conclusion has been reached. The agent-based computational approach as demonstrated in this paper proposes the possibility that in reality there may be such a wide survival range of the RRA coefficient. In addition, the time series plot of the wealth share dynamics indicates that the higher the risk aversion coefficient, the higher the wealth share. This result combined with our earlier result ([5]) well articulates the contribution of risk aversion to survivability.

Using an agent-based multi-asset artificial stock market, we simulate the survival dynamics of investors with different risk preferences. It is found that the survivability of investors is closely related to their risk preferences. Among the eight types of investors considered in this paper, only the CRRA investors with RRA coefficients close to one can survive in the long run. Other types of agents are eventually driven out of the market, including the famous CARA agents and agents who base their decision on the capital asset pricing model.

Using an agent-based multi-asset artificial stock market, we simulate the survival dynamics of investors with different risk preferences. It is found that the survivability of investors is closely related to their risk preferences. Among the eight types of investors considered in this paper, only the CRRA investors with RRA coefficients close to one can survive in the long run. Other types of agents are eventually driven out of the market, including the famous CARA agents and agents who base their decision on the capital asset pricing model.

Breast cancer is the second most common cancer in females, after lung cancer in the world. In Taiwan, there are about 8500 female suffering from breast cancer every year. The incidence of breast cancer has exceeded cervical cancer and has become the most common female cancer. Immunohistochemistry (IHC) image is widely applied to the diagnosis of breast cancer, but it requires a great deal of manpower and time. The IHC images are scoring as {0+, 1+, 2+ and 3+} corresponding to no staining, weak, moderate and strong staining, respectively. With the growing of image processing techniques, computer-assisted technologies are the best solution to reduce the variability of pathologists evaluation and provide highly specific per-cell information. Therefore, in this paper, we proposed an automatic method to assess the grade of breast cancer in IHC images. The proposed method consists of four steps, including ROI extraction, feature extraction, feature selection and a hierarchical SVM classifier. The hierarchical SVM classifier is utilized to score the IHC images into 0+ (no staining), 1+ (weak), 2+ (moderate) and 3+ (strong staining). According to the experimental results, the proposed method can automatically and effectively asses the score of IHC images; it provides important information to help physicians treat breast cancer.

s / Can J Diabetes 36 (2012) S24eS76 S57 1.29]).Nocturnalhypoglycemiawassignificantly25% lower for IDegFF vs IGlar (ERR: 0.75 [0.58; 0.97]; p1⁄40.0255), and severe hypoglycemia was 26% lower (ERR: 0.74 [0.38; 1.42]). Adverse event rates were low in both groups. Basal insulin doses did not differ; 0.40 (IDegFF) and 0.42 (IGlar) U/kg at 52 weeks. This study demonstrates that IDeg can be administered flexibly at any time of day with similar glycemic control and less nocturnal hypoglycemia than standard OD IGlar given at the same time each day over 52 weeks.

This study discusses the relationships among switching costs, inertia, and customer retention in the case of customers of banking service industries and discusses in depth whether inertia affects switching costs. In this study, we surveyed 500 existing banking account holders in Taiwan and acquired 404 valid responses. The respondents were required to submit viewpoints regarding their most familiar financial institutions. The results show that the perception of switching costs and inertia has a positive impact on banking service industries’ customer retention. Customer word of mouth is a major factor in customer retention, the attraction of new customers, and customer retention intent. Financial service providers should also attach importance to customer segmentation in order to satisfy the real needs of various types of customers and thereby increase profits and competitiveness. This paper is an important empirical analysis highlighting the significance of the effects of switching costs and inertia on customer retention in banks.