Can crumb rubber modifier effectively replace the use of polymer- modified bitumen in asphalt mixture?

Laboratory scale mechanical performances on six plant produced mixtures; three semi-dense surface courses and three dense binder courses modified with engineered crumb rubber (ECR) using the dry process are presented. The two types of mixtures produced and investigated fulfilled for the most part, the requirements of the Swiss and/or US standards regarding volumetric properties, water sensitivity and rutting. In advanced testing where no requirements exist, the dense ECR mixtures performed similar to the reference polymer modified mixtures and slightly worse for semi-dense mixtures in high temperature tests, where the binder becomes viscous in the rubber-binder composite and its ability to transfer loads is reduced. The ECR mixtures performed similarly or better than the reference in low temperature tests.  Across the advanced testing data set, all obtained results were well within acceptable values for both ECR and reference polymer mixtures indicating that crumb rubber can effectively replace polymer in asphalt mixtures

Rheological Behaviors of Waste Polyethylene Modified Asphalt Binder: Statistical Analysis of Interlaboratory Testing Results

This article investigated the effect of waste polyethylene (PE) on the modified asphalt binders' rheological behavior from a statistical point of view. The interlaboratory testing results from the RILEM Technical Committee 279 Valorization of Waste and Secondary Materials for Roads Task Group 1 were used for this purpose. First, an unaged 70/100 penetration graded neat binder was selected as the reference material. Next, a single 5 % content of waste PE additives (PE-pellets and PE-shreds) was mixed with a 95 % neat binder to prepare two PE modified binders. Then, dynamic shear rheometer-based temperature-frequency sweep tests were performed over a wide range of temperatures and frequencies to evaluate the rheological properties of these three binders. Different rheological behaviors were observed in the isochronal plots at high temperatures. Based on a reproducibility precision requirement proposed for phase angle, 28 degrees C was set as the transition temperature across the rheological behaviors. Next, according to the three rheological behaviors defined in a previous study by the authors, statistical analysis was introduced to identify sensitive rheological parameters and determine the thresholds. Results indicate that the phase angle measured above 28 degrees C and 1.59 Hz can be used as a sensitive parameter to discriminate the three rheological behaviors of PE modified binders. The thresholds among different behaviors were also calculated as an example for phase angle measured at the highest common testing temperature of 70 degrees C. Additional experimental evaluations on more types of PE modified binders, especially at intermediate and high temperatures, are recommended to better understand their influence on the rheological behavior of PE modified binders

Mechanical properties of porous asphalt, recommendations for standardization

Porous Asphalt (PA) is used worldwide for its favorable splash and spray properties and its reduction of aquaplaning under rainy conditions as well as its noise reduction properties. Switzerland started using PA in 1979 with mixed results. According to a survey taken in 2004, nine of the 26 cantons use PA. In particular, canton Vaud in western Switzerland is known as one of the leaders in promoting and using PA. Currently, 1/3 of the Vaud motorways are covered with porous asphalt and the use of PA is planned to be extended to most of the motorway surfaces in the canton Vaud up to an altitude of 600m. In addition, there are several bridge trial sections with PA. After the initial survey of the literature appropriate mechanical tests for porous asphalt were chosen (Table 8. 1). At the same time a survey of current experience with porous asphalt in Switzerland was conducted (Appendix 2). Tests were performed on laboratory prepared specimens (AG1, AG4, AG5, VD7, VD8, VD9) and cores (VD2, VD3, VD4, VD5, VS6, AG2, AG3, VD10) taken from selected pavements chosen based on the feedback from various cantons. The behavior of the selected materials was also assessed using an analytical model. Laboratory tests allowed the comparison of core performance with that of laboratory prepared specimen as well as comparison with field performance. Based on the results two mixes were optimized (VD9, AG5) and recommendations for mechanical tests appropriate for porous asphalt were made

Syngas generation from n-butane with an integrated MEMS assembly for gas processing in micro-solid oxide fuel cell systems

An integrated system of a microreformer and a carrier allowing for syngas generation from liquefied petroleum gas (LPG) for micro-SOFC application is discussed. The microreformer with an overall size of 12.7 mm × 12.7 mm × 1.9 mm is fabricated with micro-electro-mechanical system (MEMS) technologies. As a catalyst, a special foam-like material made from ceria-zirconia nanoparticles doped with rhodium is used to fill the reformer cavity of 58.5 mm3. The microreformer is fixed onto a microfabricated structure with built-in fluidic channels and integrated heaters, the so-called functional carrier. It allows for thermal decoupling of the cold inlet gas and the hot fuel processing zone. Two methods for heating the microreformer are compared in this study: a) heating in an external furnace and b) heating with the two built-in heaters on the functional carrier. With both methods, high butane conversion rates of 74%–85% are obtained at around 550 °C. In addition, high hydrogen and carbon monoxide yields and selectivities are achieved. The results confirm those from classical lab reformers built without MEMS technology (N. Hotz et al., Chem. Eng. Sci., 2008, 63, 5193; N. Hotz et al., Appl. Catal., B, 2007, 73, 336). The material combinations and processing techniques enable syngas production with the present MEMS based microreformer with high performance for temperatures up to 700°C. The functional carrier is the basis for a new platform, which can integrate the micro-SOFC membranes and the gas processing unit as subsystem of an entire micro-SOFC system

Systematic Identification of Combinatorial Drivers and Targets in Cancer Cell Lines

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance

A Reliable Method for the Selection of Exploitable Melanoma Archival Paraffin Embedded Tissues for Transcript Biomarker Profiling

The source tissue for biomarkers mRNA expression profiling of tumors has traditionally been fresh-frozen tissue. The adaptation of formalin-fixed, paraffin-embedded (FFPE) tissues for routine mRNA profiling would however be invaluable in view of their abundance and the clinical information related to them. However, their use in the clinic remains a challenge due to the poor quality of RNA extracted from such tissues. Here, we developed a method for the selection of melanoma archival paraffin-embedded tissues that can be reliably used for transcript biomarker profiling. For that, we used qRT-PCR to conduct a comparative study in matched pairs of frozen and FFPE melanoma tissues of the expression of 25 genes involved in angiogenesis/tumor invasion and 15 housekeeping genes. A classification method was developed that can select the samples with a good frozen/FFPE correlation and identify those that should be discarded on the basis of paraffin data for four reference genes only. We propose therefore a simple and inexpensive assay which improves reliability of mRNA profiling in FFPE samples by allowing the identification and analysis of “good” samples only. This assay which can be extended to other genes would however need validation at the clinical level and on independent tumor series

Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways

Signal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKKɛ, requires interaction with adapter proteins such as TRAF associated NF-κB activator (TANK). Although increased expression or dysregulation of both kinases has been described for a variety of human cancers, this study shows that deregulated expression of the TANK protein is frequently occurring in glioblastomas (GBMs). The functional relevance of TANK was analyzed in a panel of GBM-derived cell lines and revealed that knockdown of TANK arrests cells in the S-phase and prohibits tumor cell migration. Deregulated TANK expression affects several signaling pathways controlling cell proliferation and the inflammatory response. Interference with stoichiometrically assembled signaling complexes by overexpression or silencing of TANK prevented constitutive interferon-regulatory factor 3 (IRF3) phosphorylation. Knockdown of TANK frequently prevents constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). TANK-mediated ERK1/2 activation is independent from the canonical MAP kinase or ERK kinase (MEK) 1/2-mediated pathway and utilizes an alternative pathway that uses a TBK1/IKKɛ/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity.Peer reviewe

Selective BRAFV600E Inhibitor PLX4720, Requires TRAIL Assistance to Overcome Oncogenic PIK3CA Resistance

Documented sensitivity of melanoma cells to PLX4720, a selective BRAFV600E inhibitor, is based on the presence of mutant BRAFV600E alone, while wt-BRAF or mutated KRAS result in cell proliferation. In colon cancer appearance of oncogenic alterations is complex , since BRAF, like KRAS mutations, tend to co-exist with those in PIK3CA and mutated PI3K has been shown to interfere with the successful application of MEK inhibitors. When PLX4720 was used to treat colon tumours, results were not encouraging and herein we attempt to understand the cause of this recorded resistance and discover rational therapeutic combinations to resensitize oncogene driven tumours to apoptosis. Treatment of two genetically different BRAFV600E mutant colon cancer cell lines with PLX4720 conferred complete resistance to cell death. Even though p-MAPK/ ERK kinase (MEK) suppression was achieved, TRAIL, an apoptosis inducing agent, was used synergistically in order to achieve cell death by apoptosis in RKOBRAFV600E/PIK3CAH1047 cells. In contrast, for the same level of apoptosis in HT29BRAFV600E/PIK3CAP449T cells, TRAIL was combined with 17-AAG, an Hsp90 inhibitor. For cells where PLX4720 was completely ineffective, 17-AAG was alternatively used to target mutant BRAFV600E. TRAIL dependence on the constitutive activation of BRAFV600E is emphasised through the overexpression of BRAFV600E in the permissive genetic background of colon adenocarcinoma Caco-2 cells. Pharmacological suppression of the PI3K pathway further enhances the synergistic effect between TRAIL and PLX4720 in RKO cells, indicating the presence of PIK3CAMT as the inhibitory factor. Another rational combination includes 17-AAG synergism with TRAIL in a BRAFV600E mutant dependent manner to commit cells to apoptosis, through DR5 and the amplification of the apoptotic pathway. We have successfully utilised combinations of two chemically unrelated BRAFV600E inhibitors in combination with TRAIL in a BRAFV600E mutated background and provided insight for new anti-cancer strategies where the activated PI3KCA mutation oncogene should be suppressed

Narrowing the knowledge gaps for melanoma

Cutaneous melanoma originates from pigment producing melanocytes or their precursors and is considered the deadliest form of skin cancer. For the last 40 years, few treatment options were available for patients with late-stage melanoma. However, remarkable advances in the therapy field were made recently, leading to the approval of two new drugs, the mutant BRAF inhibitor vemurafenib and the immunostimulant ipilimumab. Although these drugs prolong patients' lives, neither drug cures the disease completely, emphasizing the need for improvements of current therapies. Our knowledge about the complex genetic and biological mechanisms leading to melanoma development has increased, but there are still gaps in our understanding of the early events of melanocyte transformation and disease progression. In this review, we present a summary of the main contributing factors leading to melanocyte transformation and discuss recent novel findings and technologies that will help answer some of the key biological melanoma questions and lay the groundwork for novel therapies