Efficient Spread Research Articles

Combined effects of V pits and chip size on the electrical and optical properties of green InGaN-based light-emitting diodes

The fabrication of ultra-high-resolution micro-displays with low power consumption is essential for applications in virtual reality and augmented reality systems. In this regard, GaN-based light-emitting diodes (LEDs) have been regarded as a promising candidate for self-emissive micro-displays. However, micro-LEDs suffer from sidewall defects and low quantum efficiency at a low current. Thus, we investigated the electrical and optical properties of InGaN-based green (520 nm) LEDs as functions of V pits and chip size. With decreasing chip size, the forward voltage of all samples increased at the same injection current. The samples with V pits exhibited markedly higher current density than those without V pits. With decreasing chip size, the current densities of all the samples increased, whereas the output power at the same current density decreased. As the chip size decreased, the peak external quantum efficiency of all the samples decreased, which was attained at high current densities. Furthermore, the samples with V pits displayed more efficient current spreading behavior, smaller ideality factors, and a smaller S parameter than the ones without V pits. The emission wavelength of the small samples (<300 μm) was blue-shifted with increasing current density. Based on the cathodoluminescence results, the effects of chip size, current density, and V pits on the electroluminescence spectral shift of green LEDs are described and discussed.

Highly efficient GaN-based high-power flip-chip light-emitting diodes

High-power flip-chip light-emitting diodes (FCLEDs) suffer from low efficiencies because of poor p-type reflective ohmic contact and severe current crowding. Here, we show that it is possible to improve both the light extraction efficiency (LEE) and current spreading of an FCLED by incorporating a highly reflective metallic reflector made from silver (Ag). The reflector, which consists of an Ag film covered by three pairs of TiW/Pt multilayers, demonstrates high reflectance of 95.0% at 460 nm at arbitrary angles of incidence. Our numerical simulation and experimental results reveal that the FCLED with Ag-based reflector exhibits higher LEE and better current spreading than the FCLED with indium-tin oxide (ITO)/distributed Bragg reflector (DBR). As a result, the external quantum efficiency (EQE) of FCLED with Ag-based reflector was 6.0% higher than that of FCLED with ITO/DBR at 750 mA injection current. Our work also suggests that the EQE of FCLED with the Ag-based reflector could be further enhanced 5.2% by replacing the finger-like n-electrodes with three-dimensional (3D) vias n-electrodes, which spread the injection current uniformly over the entire light-emitting active region. This study paves the way towards higher-performance LED technology.

Improved level and longevity of protective immune responses in measles virus with efficient replication in blood and lymphoid tissue

Abstract Infection with wild type measles virus (wt-MV) is an important cause of childhood mortality and is also known to induce remarkable life-long protective immunity. Despite the antigenic similarities between wt-MV and live-attenuated measles virus vaccine (LAMV), the protective immunity after measles vaccination is not as robust or long-lived. To identify mechanisms that contribute to the longevity of immune responses induced by wt-MeV infection, we compared parameters of virologic and immunologic responses after respiratory infection with wt-MeV and LAMV in rhesus macaques. Analysis of viral RNA in various tissues revealed distinct in vivo tropisms between the two strains of virus. Wt-MeV caused efficient hematogenous spread and prolonged presence of viral RNA, while LAMV caused transient localized infection in the respiratory tract. Plasma levels of cytokines IL-1β, IL-12 and interferon (IFN)-γ and chemokines CCL2, CCL11, CXCL9 and CXCL11 were increased after wt-MeV, but not LAMV infection. Infection with wt-MeV or LAMV induced comparable levels of viral-specific T cells, but significantly higher levels of protective antibody and more long-lived plasma cells were observed after wt-MeV infection. Therefore, distinct patterns of in vivo virus replication, efficiency of hematogenous spread and persistence of viral RNA are associated with the altered virulence and the level and longevity of the humoral response. Our results establish a link between life-long protective immunity and the ability of wt-MeV to spread efficiently in lymphocytes and to be cleared slowly.

Prion Efficiently Replicates in α-Synuclein Knockout Mice.

Prion diseases are a group of neurodegenerative disorders associated with the conformational conversion of the cellular prion protein (PrPC) into an abnormal misfolded form named PrPSc. Other than accumulating in the brain, PrPSc can bind PrPC and force it to change conformation to PrPSc. The exact mechanism which underlies the process of PrPC/PrPSc conversion still needs to be defined and many molecules or cofactors might be involved. Several studies have documented an important role of PrPC to act as receptor for abnormally folded forms of α-synuclein which are responsible of a group of diseases known as synucleinopathies. The presence of PrPC was required to promote efficient internalization and spreading of abnormal α-synuclein between cells. In this work, we have assessed whether α-synuclein exerts any role in PrPSc conversion and propagation either in vitro or in vivo. Indeed, understanding the mechanism of PrPC/PrPSc conversion and the identification of cofactors involved in this process is crucial for developing new therapeutic strategies. Our results showed that PrPSc was able to efficiently propagate in the brain of animals even in the absence of α-synuclein thus suggesting that this protein did not act as key modulator of prion propagation. Thus, α-synuclein might take part in this process but is not specifically required for sustaining prion conversion and propagation.

A single InGaN/GaN multiple quantum wells microwire light-emitting diode with high efficiency current injection and spreading

Micro/nanowire light-emitting diodes have inspired considerable research interests due to their wide range of potential applications, such as in micro/nanoscale display, optical communication and optical logics. To realize a single wire light-emitting diode, however, it is usually faced with low-efficiency or wavelength uncontrollable. Herein, we report on an individual coaxial core/shell InGaN/GaN microwire light-emitting diode with tunable dual-/single-wavelength light emission, which can be feasibly realized by controlling growth rate of microwires using MOCVD. The unique cross-sectional morphologies of synthesized microwires can simplify the device fabrication process and are in favor of vertical current injection and spreading simultaneously. Thus, the microwire light-emitting diodes show advantages at the suppression of efficiency droop under large current injection, with a drop ratio of 19.6%, as increasing the injection current from 2.4 A cm−2 to 92.6 A cm−2. This study proposes a core/shell multiple quantum wells microwire structure to fabricate micro light-emitting diodes which may act as a reliable light source for micro/nanoscale integrated photonic systems.

LncRNA UCA1-Mediated Cdc42 Signaling Promotes Oncolytic Vaccinia Virus Cell-to-Cell Spread in Ovarian Cancer

Oncolytic vaccinia virus (OVV) has demonstrated appropriate safety profiles for clinical development. Although designed to kill cancer cells efficiently, OVV sensitivity varies in individual cancers, and predictive biomarkers of therapeutic responses have not been identified. Here we found that OVV was much more efficient in KFTX paclitaxel-resistant ovarian cancer cells compared to that in KFlow paclitaxel-sensitive cells. Microarray analysis identified long non-coding RNA urothelial carcinoma-associated 1 (UCA1) upregulation, which contributed to both enhanced paclitaxel resistance and OVV spread. In addition, UCA1 expression correlated with efficient OVV spread in other ovarian cell lines and primary cancer cell cultures. When host pathways underlying OVV spread were analyzed, differences were detected in the activation of the Rho GTPase Cdc42, suggesting that filopodia formation enhances OVV cell-to-cell spread and tumor migration. Moreover, we established a clinically relevant mouse model of peritoneal metastasis using KFTX or KFlow cells. Paclitaxel exerted anti-tumor effects on KFlow, but not KFTX, tumors. In mice bearing KFTX cells after paclitaxel failure, OVV treatment induced the regression of residual tumors and improved survival. Our findings demonstrated that UCA1 promotes OVV cell-to-cell spread in ovarian cancer, resulting in enhanced therapeutic outcome.

Pancharatnam–Berry optical lenses

In this paper, we analyze a few aspects of Pancharatnam–Berry (PB) phase optical lenses. First, we provide theoretical formulas on how the optical efficiency, focal length, and point spread function depend on wavelength and validate them with numerical calculations based on Fresnel diffraction theory. Second, we perform numerical studies on how optical efficiency is affected by discretization of the PB phase. We find that phase discretization significantly lowers the optical efficiency for low f-number PB lenses.

In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics.

Tumor therapy with replication competent viruses is an exciting approach to cancer eradication where viruses are engineered to specifically infect, replicate, spread and kill tumor cells. The outcome of tumor virotherapy is complex due to the variable interactions between the cancer cell and virus populations as well as the immune response. Oncolytic viruses are highly efficient in killing tumor cells in vitro, especially in a 2D monolayer of tumor cells, their efficiency is significantly lower in a 3D environment, both in vitro and in vivo. This indicates that the spatial dimension may have a major influence on the dynamics of virus spread. We study the dynamic behavior of a spatially explicit computational model of tumor and virus interactions using a combination of in vitro 2D and 3D experimental studies to inform the models. We determine the number of nearest neighbor tumor cells in 2D (median = 6) and 3D tumor spheroids (median = 16) and how this influences virus spread and the outcome of therapy. The parameter range leading to tumor eradication is small and even harder to achieve in 3D. The lower efficiency in 3D exists despite the presence of many more adjacent cells in the 3D environment that results in a shorter time to reach equilibrium. The mean field mathematical models generally used to describe tumor virotherapy appear to provide an overoptimistic view of the outcomes of therapy. Three dimensional space provides a significant barrier to efficient and complete virus spread within tumors and needs to be explicitly taken into account for virus optimization to achieve the desired outcome of therapy.

Light-emitting diodes with surface gallium nitride p\u2013n homojunction structure formed by selective area regrowth

In this study, the blue light-emitting diode (LED) structures based on gallium nitride (GaN) were presented. Each structure possessed a surface GaN p–n junction, which was formed through selective area regrowth on an InGaN/GaN multiple quantum well (MQW) structure and served as the carrier injector. The LEDs that showed efficient hole injection and current spreading were configured to form a p-type GaN layer between the MQW and regrown n-type GaN top layer. These LEDs exhibited higher luminous efficiency and lower operation voltage than the LEDs with regrown p-type GaN top layers. The LEDs with n-type GaN top layers emitted single-peak spectra at approximately 450 nm under a forward bias. The UV peak at 365 nm (i.e., the GaN band-edge emission) was absent because the regrown surface GaN p–n junctions behaved as carrier injectors rather than photon injectors. In other words, the single-peak blue emission was not generated by the optical pumping of UV light emitted from the surface p–n GaN homojunction.

Temporal information gathering process for node ranking in time-varying networks.

Many systems are dynamic and time-varying in the real world. Discovering the vital nodes in temporal networks is more challenging than that in static networks. In this study, we proposed a temporal information gathering (TIG) process for temporal networks. The TIG-process, as a node's importance metric, can be used to do the node ranking. As a framework, the TIG-process can be applied to explore the impact of temporal information on the significance of the nodes. The key point of the TIG-process is that nodes' importance relies on the importance of its neighborhood. There are four variables: temporal information gathering depth n, temporal distance matrix D, initial information c, and weighting function f. We observed that the TIG-process can degenerate to classic metrics by a proper combination of these four variables. Furthermore, the fastest arrival distance based TIG-process ( fad-tig) is performed optimally in quantifying nodes' efficiency and nodes' spreading influence. Moreover, for the fad-tig process, we can find an optimal gathering depth n that makes the TIG-process perform optimally when n is small.

Efficient performance enhancement of GaN-based vertical light-emitting diodes coated with N-doped graphene quantum dots

Novel vertical light-emitting diodes (VLEDs) decorated with N-doped graphene quantum dots (N-GQDs) have been fabricated, based on the metal organic chemical vapor deposition method (MOCVD), wafer bonding technique, laser lift-off (LLO) technique, inductively coupled plasma (ICP) etching and impregnation processing. There is an obvious luminescence enhancement and resistance reduction for VLEDs after coating N-GQDs. The results show an improvement of light output power (LOP), dependent on the improvement of optical extraction efficiency and current spreading. The improvement of external quantum efficiency (EQE) is mainly owing to the roughened surfaces. Meanwhile, an enhancement of electroluminescence (EL) intensity and photoluminescence (PL) intensity has been achieved when the VLEDs were immersed in 0.9 mg/mL of N-GQDs solution, 4 times that of bare VLEDs. After coating N-GQDs, the performance of VLEDs is greatly improved, which could be attributed to the photons recovered by extracting light from waveguide modes.

The Many Faces of Emerging and Reemerging Infectious Disease.

The emergence of disease threats can take many forms, from the adaptation of a traditionally zoonotic pathogen for efficient spread in humans, to the development of antibiotic resistance in well-known pathogens, to the creation of new niches for established disease through social and societal changes. In this commentary, the authors explore these various facets of disease emergence through the lens of the papers included in this issue of Epidemiologic Reviews. The authors explore multiple aspects of emergence and the ways in which emergent pathogens can be controlled with the limited tools available. In doing so, they put the papers in this issue in the context of the broader research agenda around understanding and combatting emergent pathogens.

Targeting the tumor stroma with an oncolytic adenovirus secreting a fibroblast activation protein-targeted bispecific T-cell engager

BackgroundOncolytic virus (OV)-based therapies have an emerging role in the treatment of solid tumors, involving both direct cell lysis and immunogenic cell death. Nonetheless, tumor-associated stroma limits the efficacy of oncolytic viruses by forming a barrier that blocks efficient viral penetration and spread. The stroma also plays a critical role in progression, immunosuppression and invasiveness of cancer. Fibroblast activation protein-α (FAP) is highly overexpressed in cancer-associated fibroblasts (CAFs), the main cellular component of tumor stroma, and in this study we assessed whether arming oncolytic adenovirus (OAd) with a FAP-targeting Bispecific T-cell Engager (FBiTE) could retarget infiltrated lymphocytes towards CAFs, enhancing viral spread and T cell-mediated cytotoxicity against the tumor stroma to improve therapeutic activity.MethodsThe bispecific T-cell Engager against FAP was constructed using an anti-human CD3 single-chain variable fragment (scFv) linked to an anti-murine and human FAP scFv. This FBiTE was inserted in the oncolytic adenovirus ICOVIR15K under the control of the major late promoter, generating the ICO15K-FBiTE. ICO15K-FBiTE replication and potency were assessed in HT1080 and A549 tumor cell lines. The expression of the FBiTE and the activation and proliferation of T cells that induced along with the T cell-mediated cytotoxicity of CAFs were evaluated by flow cytometry in vitro.In vivo, T-cell biodistribution and antitumor efficacy studies were conducted in NOD/scid/IL2rg−/− (NSG) mice.ResultsFBiTE expression did not decrease the infectivity and replication potency of the armed virus. FBiTE-mediated binding of CD3+ effector T cells and FAP+ target cells led to T-cell activation, proliferation, and cytotoxicity of FAP-positive cells in vitro. In vivo, FBiTE expression increased intratumoral accumulation of T cells and decreased the level of FAP, a marker of CAFs, in tumors. The antitumor activity of the FBiTE-armed adenovirus was superior to the parental virus.ConclusionsCombination of viral oncolysis of cancer cells and FBiTE-mediated cytotoxicity of FAP-expressing CAFs might be an effective strategy to overcome a key limitation of oncolytic virotherapy, encouraging its further clinical development.

An Efficient Spreading Strategy Considering Information Decays and Partial Interactions Between People in Scale-Free Networks

Complex networks are extensively applied to study the dynamics of real systems, such as how information spreads in social networks. Most existing spreading strategies are studied based on simple information spreading model, such as the optimized compartmental models in epidemics. However, for information spreading in social networks, more complex social factors should be considered. In this paper, we build an information spreading model that involves information decays and partial interactions based on multi-agent modeling in scale-free networks. The positive effects of a set of vertices on the spreading efficiency are discovered based on the proposed information spreading model. On the basis of the positive effects of those vertices, we propose an efficient spreading strategy for extending the spreading in scale-free networks. Ten groups of Monte Carlo experiments are conducted to verify the effectiveness of the proposed strategy. The experimental results demonstrated the effectiveness and validity of the proposed strategy. The proposed strategy can be exploited to extend the spread of warnings or control the spread of rumors in social networks.

English

English

95P - Targeting the tumor stroma with a bispecific T-cell engager-armed oncolytic adenovirus

Background: Oncolytic virus (OV)-based therapies have an emerging role in the treatment of solid tumors, involving both direct cell lysis and immunogenic cell death. Nonetheless, tumor-associated stroma limits the efficacy of OVs by forming a barrier that blocks efficient viral penetration and spread. Moreover, the stroma plays a critical role in progression and immunosuppression of cancer. Fibroblast activation protein-α (FAP) is highly overexpressed in cancer-associated fibroblasts (CAFs), the main cellular component of tumor stroma, and in this study we assessed whether arming oncolytic adenovirus (OAd) with a FAP-targeting Bispecific T-cell Engager (FBiTE) could retarget infiltrated lymphocytes towards CAFs, enhancing viral spread and anti-tumor immunity to improve therapeutic activity. Methods: The BiTE against FAP was constructed using an anti-human CD3 single-chain variable fragment (scFv) linked to an anti-murine and human FAP scFv. This FBiTE was inserted in the oncolytic adenovirus ICOVIR15K under the control of the major late promoter, generating the ICO15K-FBiTE. ICO15K-FBiTE replication and potency were assessed in HT1080 and A549 tumor cell lines. The expression of the FBiTE and the activation and proliferation of T cells that induced along with the T-cell-mediated cytotoxicity of CAFs were evaluated by flow cytometry in vitro. In vivo T-cell biodistribution and antitumor efficacy studies were conducted in NOD/scid/IL2rg-/- (NSG) mice. Results: FBiTE expression from the OAd ICO15K did not decrease the infectivity and replication potency in vitro. T-cells activation and proliferation, leading to T-cells-mediated cytotoxicity of FAP-positive cells was successfully achieved after FBiTE-mediated binding of both CD3+cells and FAP+ cells. In vivo, FBiTE expression increased intratumoral accumulation of T-cells and decreased the level of FAP, a marker of CAFs, in tumors. The antitumor activity of the FBiTE-armed OAd was superior to the parental virus. Conclusions: Combination of viral oncolysis of cancer cells and FBiTE-mediated cytotoxicity of FAP-expressing CAFs might be an effective strategy to overcome a key limitation of oncolytic virotherapy, encouraging its further clinical development. Legal entity responsible for the study: IDIBELL. Funding: Ministerio de Economía y Competividad and Generalitat de Catalunya. Disclosure: All authors have declared no conflicts of interest.

Herpes Simplex Virus 1 Deregulation of Host MicroRNAs.

Viruses utilize microRNAs (miRNAs) in a vast variety of possible interactions and mechanisms, apparently far beyond the classical understanding of gene repression in humans. Likewise, herpes simplex virus 1 (HSV-1) expresses numerous miRNAs and deregulates the expression of host miRNAs. Several HSV-1 miRNAs are abundantly expressed in latency, some of which are encoded antisense to transcripts of important productive infection genes, indicating their roles in repressing the productive cycle and/or in maintenance/reactivation from latency. In addition, HSV-1 also exploits host miRNAs to advance its replication or repress its genes to facilitate latency. Here, we discuss what is known about the functional interplay between HSV-1 and the host miRNA machinery, potential targets, and the molecular mechanisms leading to an efficient virus replication and spread.

Vaccinia virus hijacks EGFR signalling to enhance virus spread through rapid and directed infected cell motility.

Introductory paragraphCell motility is essential for viral dissemination1. Vaccinia virus (VACV), a close relative of smallpox virus, is thought to exploit cell motility as a means to enhance the spread of infection1. A single viral protein, F11L, contributes to this by blocking RhoA signalling to facilitate cell retraction2. However, F11L alone is not sufficient for VACV induced cell motility, indicating that additional viral factors must be involved. Here we show that the VACV epidermal growth factor homolog, VGF, promotes infected cell motility and the spread of viral infection. We found that VGF secreted from early infected cells is cleaved by ADAM10 whereupon it acts largely in a paracrine fashion to direct cell motility at the leading edge of infection. Real-time tracking of cells infected in the presence of EGFR/MAPK/FAK/ADAM10 inhibitors, or with VGF and F11 deleted viruses, revealed defects in radial velocity and directional migration efficiency leading to impaired cell-to-cell spread of infection. Furthermore, intravital imaging showed that virus spread and lesion formation are attenuated in the absence of VGF. Our results demonstrate how poxviruses hijack epidermal growth factor receptor induced cell motility to promote rapid and efficient spread of infection in vitro and in vivo.

Magnetic Field-Induced Assembly of Superparamagnetic Cobalt Nanoparticles on Substrates and at Liquid-Air Interface.

Superparamagnetic cobalt nanoparticles (Co NPs) are an interesting material for self-assembly processes because of their magnetic properties. We investigated the magnetic field-induced assembly of superparamagnetic cobalt nanoparticles and compared three different approaches, namely, the assembly on solid substrates, at water-air, and ethylene glycol-air interfaces. Oleic acid- and trioctylphosphine oxide-coated Co NPs were synthesized via a thermolysis of cobalt carbonyl and dispersed into either hexane or toluene. The Co NP dispersion was dropped onto different substrates (e.g., transmission electron microscopy (TEM) grid, silicon wafer) and onto liquid surfaces. Transmission electron microscopy (TEM), scanning force microscopy, optical microscopy, as well as scanning electron microscopy showed that superparamagnetic Co NPs assembled into one-dimensional chains in an external magnetic field. By varying the concentration of the Co NP dispersion (1-5 mg/mL) and the strength of the magnetic field (4-54 mT), the morphology of the chains changed. Short, thin, and flexible chain structures were obtained at low NP concentration and low strength of magnetic field, whereas they became long, thick and straight when the NP concentration and the magnetic field strength increased. In comparison, the assembly of Co NPs from hexane dispersion at ethylene glycol-air interface showed the most regular and homogeneous alignment, since a more efficient spreading could be achieved on ethylene glycol than on water and solid substrates.

Dual-vector prodrug activator gene therapy using retroviral replicating vectors

Retroviral replicating vectors (RRVs) have been shown to achieve efficient tumor transduction and enhanced therapeutic benefits in a variety of cancer models. In the present study, we evaluated a possible combinatorial effect of prodrug activator genes delivered by two different RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV) on human hepatocellular carcinoma Hep3B cells. Both RRVs showed efficient replicative spread in culture and can overcame superinfection resistance each other. Notably, the replication and spread of each RRV in culture remained unaffected by pretransduction with the counterpart RRV. We further transduced cells with RRVs which individually possessed the prodrug activator genes yeast cytosine deaminase (CD) and herpes simplex virus thymidine kinase (TK) alone or in combination, and evaluated the cytotoxic effects of RRV-mediated gene therapy with CD and TK in the presence of the respective prodrugs, 5-fluorocytosine and ganciclovir. All combinations of the two prodrug activator genes produced synergistic cytocidal effects, but the combined effects of the different genes were significantly greater than those of the same genes when delivered by two different vectors. The present findings indicate the potential utility of dual-vector gene therapy using two different RRVs carrying different prodrug activator genes.