Bridge percolation: electrical connectivity of discontinued conducting slabs by metallic nanowires.

The properties of nanostructured networks of conductive materials have been extensively studied under the lens of percolation theory. In this work, we introduce a novel type of local percolation phenomenon used to investigate the conduction properties of a new hybrid material that combines sparse metallic nanowire networks and fractured conducting thin films on flexible substrates. This original concept could potentially lead to the design of a novel composite transparent conducting material. Using a complementary approach including formal analytical derivations, Monte Carlo simulations and electrical circuit representation for the modelling of bridged-percolating nanowire networks, we unveil the key relations between linear crack density, nanowire length and network areal mass density that ensure electrical percolation through the hybrid. The proposed theoretical model provides key insights into the conduction mechanism associated with the original concept of bridge percolation in random nanowire networks.

Understanding the mechanisms leading to failure in metallic nanowire-based transparent heaters, and solution for stability enhancement.

Silver nanowire (AgNW) networks are emerging as one of the most promising alternatives to indium tin oxide (ITO) for transparent electrodes in flexible electronic devices. They can be used in a variety of optoelectronic applications such as solar cells, touch panels and organic light-emitting diodes. Recently they have also proven to be very efficient when used as transparent heaters (THs). In addition to the study of AgNW networks acting as THs in regular use, i.e. at low voltage and moderate temperature, their stability and physical behavior at higher voltages and for longer durations should be studied in view of their integration into real devices. The properties of AgNW networks deposited by spray coating on glass or flexible transparent substrates are thoroughly studied via in situ measurements. The AgNW networks' behavior at different voltages for different durations and under different atmospheric conditions, both in air and under vacuum, has been examined. At low voltage, a reversible electrical response is observed while irreversibility and even failure are observed at higher voltages. In order to gain a deeper insight into the behavior of AgNW networks used as THs, simple but realistic physical models are proposed and are found to be in fair agreement with the experimental data. Finally, as the stability of AgNW networks is a key issue, we demonstrate that coating AgNW networks with a very thin layer of TiO2 using atomic layer deposition (ALD) improves the material's resistance against electrical and thermal instabilities without altering optical transmittance. We show that the critical annealing temperature associated to network breakdown increases from 270 °C for the as-deposited AgNW networks to 420 °C for AgNW networks coated with TiO2. Similarly, the electrical failure which occurs at 7 V for the as-deposited networks increases to 13 V for TiO2-coated networks. TiO2 is also proved to stabilize AgNW networks during long duration operation and at high voltage. Temperature higher than 235 °C was achieved at 7 V without failure.

Optimization of silver nanowire-based transparent electrodes: effects of density, size and thermal annealing.

Silver nanowire (AgNW) networks are efficient as flexible transparent electrodes, and are cheaper to fabricate than ITO (Indium Tin Oxide). Hence they are a serious competitor as an alternative to ITO in many applications such as solar cells, OLEDs, transparent heaters. Electrical and optical properties of AgNW networks deposited on glass are investigated in this study and an efficient method to optimize them is proposed. This paper relates network density, nanowire dimensions and thermal annealing directly to the physical properties of the nanowire networksusing original physical models. A fair agreement is found between experimental data and the proposed models. Moreover thermal stability of the nanowires is a key issue in thermal optimization of such networks and needs to be studied. In this work the impact of these four parameters on the networks physical properties are thoroughly investigated via in situ measurements and modelling, such a method being also applicable to other metallic nanowire networks. We demonstrate that this approach enables the optimization of both optical and electrical properties through modification of the junction resistance by thermal annealing, and a suitable choice of nanowire dimensions and network density. This work reports excellent optical and electrical properties of electrodes fabricated from AgNW networks with a transmittance T = 89.2% (at 550 nm) and a sheet resistance of Rs = 2.9 Ω â–¡(-1), leading to the highest reported figure of merit.

Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells.

BACKGROUND: The sequence of the beta-subunit of human chorionic gonadotropin (hCGß) varies depending on whether hCGß is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCGß can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCGß encoded by type II genes (type II hCGß). METHODS: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCGß dosing immunoassays and sequencing of CGB genes were performed. RESULTS: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCGß derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and T24 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCGß. Placenta immunohistochemical studies confirmed that type II hCGß expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCGß in serum of patients with either nontrophoblastic cancers or fetal Down syndrome. CONCLUSION: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.

Metallic nanowire networks: effects of thermal annealing on electrical resistance.

Metallic nanowire networks have huge potential in devices requiring transparent electrodes. This article describes how the electrical resistance of metal nanowire networks evolve under thermal annealing. Understanding the behavior of such films is crucial for the optimization of transparent electrodes which find many applications. An in-depth investigation of silver nanowire networks under different annealing conditions provides a case study demonstrating that several mechanisms, namely local sintering and desorption of organic residues, are responsible for the reduction of the systems electrical resistance. Optimization of the annealing led to specimens with transmittance of 90% (at 550 nm) and sheet resistance of 9.5 Ω sq(-1). Quantized steps in resistance were observed and a model is proposed which provides good agreement with the experimental results. In terms of thermal behavior, we demonstrate that there is a maximum thermal budget that these electrodes can tolerate due to spheroidization of the nanowires. This budget is determined by two main factors: the thermal loading and the wire diameter. This result enables the fabrication and optimization of transparent metal nanowire electrodes for solar cells, organic electronics and flexible displays.

A short-term colorectal cancer sphere culture as a relevant tool for human cancer biology investigation.

BACKGROUND: Ex vivo colospheres have been previously characterised as a colorectal cancer (CRC) well-rounded multicellular model, exclusively formed by carcinoma cells, and derived from fresh CRC tissue after mechanical dissociation. The ability to form colospheres was correlated with tumour aggressiveness. Their three-dimensional conformation prompted us to further investigate their potential interest as a preclinical cancer tool. METHODS: Patient-derived CRC xenografts were used to produce numerous colospheres. Mechanism of formation was elucidated by confocal microscopy. Expression analysis of a panel of 64 selected cancer-related genes by real-time qRT-PCR and hierarchical clustering allowed comparison of colospheres with parent xenografts. In vitro and in vivo assays were performed for migration and chemosensitivity studies. RESULTS: Colospheres, formed by tissue remodelling and compaction, remained viable several weeks in floating conditions, escaping anoikis through their strong cell-cell interactions. Colospheres matched the gene expression profile of the parent xenograft tissue. Colosphere-forming cells migrated in collagen I matrix and metastasised when subrenally implanted in nude mice. Besides, the colosphere responses to 5-fluorouracil and irinotecan, two standard drugs in CRC, reproduced those of the in vivo original xenografts. CONCLUSION: Colospheres closely mimic biological characteristics of in vivo CRC tumours. Consequently, they would be relevant ex vivo CRC models.

Film-thickness-dependent conduction in ordered Si quantum dot arrays.

In recent years, silicon nanostructures have been investigated extensively for their potential use in photonic and photovoltaic applications. So far, for silicon quantum dots embedded in SiO(2), control over inter-dot distance and size has only been observed in multiple bilayer stacks of silicon-rich oxides and silicon dioxide. In this work, for the first time the fabrication of spatially well-ordered Si quantum dots (QDs) in SiO(2) is demonstrated, without using the multilayer approach. This ordered formation, confirmed with TEM micrographs, depends on the thickness of the initially deposited sub-stoichiometric silicon oxide film. Grazing incidence x-ray diffraction confirms the crystallinity of the 5 nm QDs while photoluminescence shows augmented bandgap values. Low-temperature current-voltage measurements demonstrate film thickness and order-dependent conduction mechanisms, showing the transition from temperature-dependent conduction in randomly placed dots to temperature-independent tunnelling for geometrically ordered nanocrystals. Contrary to expectations from dielectric materials, significant conduction and photocarrier generation have been observed in our Si QDs embedded in SiO(2) demonstrating the possibility of forming initial film-thickness-controlled conductive films. This conduction via the silicon quantum dots in thick single layers is a promising result for integration into photovoltaic devices.

Newly characterised ex vivo colospheres as a three-dimensional colon cancer cell model of tumour aggressiveness.

BACKGROUND: New models continue to be required to improve our understanding of colorectal cancer progression. To this aim, we characterised in this study a three-dimensional multicellular tumour model that we named colospheres, directly obtained from mechanically dissociated colonic primary tumours and correlated with metastatic potential. METHODS: Colorectal primary tumours (n=203) and 120 paired non-tumoral colon mucosa were mechanically disaggregated into small fragments for short-term cultures. Features of tumours producing colospheres were analysed. Further characterisation was performed using colospheres, generated from a human colon cancer xenograft, and spheroids, formed on agarose by the paired cancer cell lines. RESULTS: Colospheres, exclusively formed by viable cancer cells, were obtained in only 1 day from 98 tumours (47%). Inversely, non-tumoral colonic mucosa never generated colospheres. Colosphere-forming capacity was statistically significantly associated with tumour aggressiveness, according to AJCC stage analysis. Despite a close morphology, colospheres displayed higher invasivity than did spheroids. Spheroids and colospheres migrated into Matrigel but matrix metalloproteinase (MMP)-2 and MMP-9 activity was detected only in colospheres. Mouse subrenal capsule assay revealed the unique tumorigenic and metastatic phenotype of colospheres. Moreover, colospheres and parental xenograft reproduced similar CD44 and CD133 expressions in which CD44+ cells represented a minority subset of the CD133+ population. CONCLUSION: The present colospheres provide an ex vivo three-dimensional model, potentially useful for studying metastatic process.

Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts.

Trophoblast research over the past decades has underlined the striking similarities between the proliferative, migratory and invasive properties of placental cells and those of cancer cells. This review recapitulates the numerous key molecules, proto-oncogenes, growth factors, receptors, enzymes, hormones, peptides and tumour-associated antigens (TAAs) expressed by both trophoblastic and cancer cells in an attempt to evaluate the genes and proteins forming molecular circuits and regulating the similar behaviours of these cells. Among the autocrine and paracrine loops that might be involved in the strong proliferative capacity of trophoblastic and cancer cells, epidermal growth factor (EGF)/EGF receptor (EGFR), hepatocyte growth factor (HGF)/HGF receptor (HGFR) (Met) and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) loops may play a predominant role. Similar mechanisms of migration and invasion displayed by trophoblastic and malignant cells comprise alterations in the adhesion molecule phenotype, including the increased expression of alpha1beta1 and alphavbeta3 integrin receptors, whereas another critical molecular event is the down-regulation of the cell adhesion molecule E-cadherin. Among proteases that may play an active role in the invasive capacities of these cells, accumulating evidence suggests that matrix metalloproteinase-9 (MMP-9) expression/activation is a prerequisite. Finally, an overview of molecular circuitries shared by trophoblast and cancer cells reveals that the activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT axis has recently emerged as a central feature of signalling pathways used by these cells to achieve their proliferative, migratory and invasive processes.

Expression of early placenta insulin-like growth factor in breast cancer cells provides an autocrine loop that predominantly enhances invasiveness and motility.

Early placenta insulin-like growth factor (EPIL) is expressed by a subpopulation of the Her2-positive SKBR3 breast cancer cell line displaying high motility and transendothelial invasiveness in vitro, as recently shown by our group. As a consequence of this, we established cellular models by generating an EPIL-overexpressing SKBR3 cell line, knocked down EPIL by adding specific small interfering RNA (siRNA) to those cells and produced EPIL-enriched and depleted serum-free culture media. EPIL-expressing cells as well as EPIL-induced SKBR3 cells acquired a high capacity for transendothelial invasiveness. We observed a thin and outspread morphology caused by enhanced formation of lamellipodia, i.e. protrusions in the initial phase of motility. In parallel, Her2-positive MDAHer2 breast cancer cells also showed increased invasiveness when induced by EPIL-conditioned medium. A downstream signaling impact of EPIL could be observed in the form of reduced phosphorylation of Her2, erk1/2 and akt, while phospholipase Cgamma1 phophorylation remained unaffected. As an in vivo model for highly motile tumor cells, Paget's disease of the nipple showed simultaneous EPIL and Her2 expression upon immunohistochemical examination using specific antibodies. Such experimental data have been translated to a clinical setting by using a prognostic tissue microarray established from 603 breast cancer cases. Survival data analysis found a significant association between expression levels of EPIL and 5-year overall survival that was dose dependent: EPIL (negative) 84%, EPIL (moderately positive) 77%, EPIL (strongly positive) 48% (P < 0.005). One particular subgroup (7.6% of the cases with full clinical records) that comprised tumors simultaneously expressing EPIL and Her2 represented patients with the poorest 5-year overall survival. The results suggested that EPIL might be a cancer cell-produced growth factor that influences lateral Her2 signaling. Moreover, EPIL may be induced by factors apart from Her2 and may independently provide signaling for cancer invasion and motility.

Direct evidence of nanometric invasionlike grain boundary penetration in the A(1)/Ga system.

We report the first in situ results of deformation during grain boundary penetration in the A(1)/Ga system, obtained with a novel, nondestructive hard x-ray synchrotron projection microscopy technique. Focusing the beam to a state-of-the-art spot size of 90 x 90 nm(2), we demonstrate that penetration is accompanied by continuous relative separation of the Al grains of the same final amplitude as the final Ga layer thickness in the absence of external stress. The formation of nanometric intergranular liquid layers is originated by a crack propagation process and inherently implies the presence of weak stress levels.

Bcl-2 and CCND1/CDK4 expression levels predict the cellular effects of mTOR inhibitors in human ovarian carcinoma.

Molecular markers enabling the prediction of sensitivity/resistance to rapamycin may facilitate further clinical development of rapamycin and its derivatives as anticancer agents. In this study, several human ovarian cancer cell lines (IGROV1, OVCAR-3, A2780, SK-OV-3) were evaluated for susceptibility to rapamycin-mediated growth inhibition. The differential expression profiles of genes coding for proteins known to be involved in the mTOR signaling pathway, cell cycle control and apoptosis were studied before and after drug exposure by RT-PCR. In cells exposed to rapamycin, we observed a dose-dependent downregulation of CCND1 (cyclin D1) and CDK4 gene expression and late G1 cell cycle arrest. Among these cell lines, SK-OV-3 cells resistant to both rapamycin and RAD001 were the sole to show the expression of the anti-apoptotic gene Bcl-2. Bcl-2/bclxL-specific antisense oligonucleotides restored the sensitivity of SK-OV-3 cells to apoptosis induction by rapamycin and RAD001. These results indicate that baseline Bcl-2 expression and therapy-induced downexpression of CCND1 and CDK4 may be regarded as molecular markers enabling the prediction and follow-up of the cellular effects on cell cycle and apoptosis induction of rapamycin in ovarian cancer. Furthermore, strategies to down regulate Bcl-2 in ovarian cancer may prove useful in combination with rapamycin or RAD001 for ovarian cancer.

Tumor escape from killing: role of killer inhibitory receptors and acquisition of tumor resistance to cell death.

Immunotherapy of cancer has always been a very attractive fourth-modality therapeutic approach. Over the past few years, advances in the identification of tumor antigens have offered new perspectives and provided new opportunities for more accurate immunotherapy for cancer. However, when applied to patients with established tumors, it rarely leads to an objective response. This is partly due to the fact that tumors evade host immunity at both the induction and effector phases. Thus, understanding tumor escape mechanisms may be the key to successful immunotherapy for cancer. In the present review, we will focus on how the expression of killer Ig receptors (KIR) on tumor infiltrating lymphocytes can compromise their function and how tumors evade apoptotic death - two additional mechanisms of tumor escape.

Gene expression profiles of bladder cancers: evidence for a striking effect of in vitro cell models on gene patterns.

In order to assess the effect of in vitro models on the expression of key genes known to be implicated in the development or progression of cancer, we quantified by real-time quantitative PCR the expression of 28 key genes in three bladder cancer tissue specimens and in their derived cell lines, studied either as one-dimensional single cell suspensions, two-dimensional monolayers or three-dimensional spheroids. Global analysis of gene expression profiles showed that in vitro models had a dramatic impact upon gene expression. Remarkably, quantitative differences in gene expression of 2-63-fold were observed in 24 out of 28 genes among the cell models. In addition, we observed that the in vitro model which most closely mimicked in vivo mRNA phenotype varied with both the gene and the patient. These results provide evidence that mRNA expression databases based on cancer cell lines, which are studied to provide a rationale for selection of therapy on the basis of molecular characteristics of a patient's tumour, must be carefully interpreted.

Quantification of human cytomegalovirus DNA in bone marrow transplant recipients by real-time PCR.

A real-time PCR assay was developed to quantify human cytomegalovirus (CMV) DNA in peripheral blood leukocytes (PBLs) of bone marrow transplantation patients. Unlike other teams, we quantified CMV and the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene using a plasmid containing both sequences as an external standard. Tenfold serial dilutions of this plasmid yielded overlapping standard curves that allowed the quantification of CMV and GAPDH gene copies in an efficient and accurate manner. Sequential blood samples (164 specimens) were collected from 16 patients. PBLs were tested by the pp65 antigenemia assay and quantitative CMV and GAPDH gene PCRs. CMV DNA was detected by PCR in 13 patients a mean of 15 days prior to the appearance of antigenemia. The administration of anti-CMV drugs led to a rapid decrease in the numbers of viral copies and positive nuclei. Real-time PCR assay results correlated with those of the CMV pp65 antigenemia assay (P < 0.00001). The TaqMan assay may be a useful tool for rapid quantification of CMV infection and for monitoring of CMV reactivation in bone marrow transplantation recipients.

Analysis of interleukin-18, interleukin-1 converting enzyme (ICE) and interleukin-18-related cytokines in Crohn's disease lesions.

A local increase of interleukin-18 (IL-18) expression has been recently demonstrated in Crohn's disease (CD), suggesting a role for mature IL-18 (cleaved by ICE protease) in the induction of proinflammatory cytokines and Th1 polarization observed in CD lesions. The aim of this study was to investigate IL-18 modulation and its potential immune consequences in CD lesions. We showed increased IL-18 production in chronic CD lesions and identified epithelial cells and macrophages as IL-18-producing cells. A twofold increase in ICE alpha, beta, and/or gamma mRNA that encodes for the complete mature peptide was required for ICE activity, and a marked increase in IL-18R-positive immune cells was observed in chronic lesions compared to uninvolved areas or normal control samples. Chronic lesions also displayed intense transcription of IL-18-induced cytokines, IFN-gamma, IL-1beta, TNF-alpha, and IL-8. By contrast, when neither IL-18 nor ICE mRNAs were enhanced (early asymptomatic CD lesions), IL-18-induced cytokines were not up-regulated. These results are in accordance with a putative role of mature IL-18 in the pathogenesis of CD.