Enhanced sensitivity detection of protein immobilization by fluorescent interference on oxidized silicon.

We present a silicon chip-based approach for the enhanced sensitivity detection of surface-immobilized fluorescent molecules. Green fluorescent protein (GFP) is bound to the silicon substrate by a disuccinimidyl terephtalate-aminosilane immobilization procedure. The immobilized organic layers are characterized by surface analysis techniques, like ellipsometry, atomic force microscopy (AFM) and X-ray induced photoelectron spectroscopy. We obtain a 20-fold enhancement of the fluorescent signal, using constructive interference effects in a fused silica dielectric layer, deposited before immobilization onto the silicon. Our method opens perspectives to increase by an order of magnitude the fluorescent response of surface immobilized DNA- or protein-based layers for a variety of biosensor applications.

Thermodynamic investigations in the Si-Ge-rich part of the ruthenium-silicon-germanium system

This paper reports molar heat capacities of Ru50SixGe(50-x) and Ru40SiyGe(60-y) ternary solid solutions determined by differential scanning calorimetry. A second order transition has been characterised for alloys ranging from Ru40Ge60 to Ru40Si10Ge50 at temperatures ranging from 850 to 1040 K, respectively. Tie lines have been established at 1000-900-800-700-600 degrees C by electron microprobe measurements on annealed alloys of the two phase domains: Ru50SixGe(50-x)-Ru40SiyGe(60-y) and Ru40SiyGe(60-y)-SizGe(100-z).

Bridge to life: the Lifebridge B2T extracorporeal life support system in an in vitro trial.

Extracorporeal life support systems (ECLS) have become common in cardiothoracic surgery, but are still "Terra Incognita" in other medical fields due to the fact that perfusion units are normally bound to cardiothoracic centres. The Lifebridge B2T is an ECLS that is meant to be used as an easy and fast-track extracorporeal cardiac support to provide short-term perfusion for the transport of a patient to a specialized centre. With the Lifebridge B2T it is now possible to provide extracorporeal bypass for patients in hospitals without a perfusion unit. The Lifebridge B2T was tested on three calves to analyze the handling, performance and security of this system. The Lifebridge B2T safely can be used clinically and can provide full extracorporeal support for patients in cardiac or pulmonary failure. Flows up to 3.9 +/- 0.2l/min were reached, with an inflow pressure of -103 +/- 13mmHg, using a 21Fr. BioMedicus (Medtronic, Minneapolis, MN, USA) venous cannula. The "Plug and Play" philosophy, with semi-automatic priming, integrated check-list, a long battery time of over two hours and instinctively designed user interface, makes this device very interesting for units with high-risk interventions, such as catheterisation labs. If a system is necessary in an emergency unit, the Lifebridge can provide a high security level, even in centres not acquainted with cardiopulmonary bypass.

The ruthenium-silicon system

The Ruthenium-Silicon system has been completely revised using differential thermal analysis, X-ray diffraction and electron microprobe investigations. The two equiatomic compound structures (CsCl and FeSi types) have been identified as two different phases. The occurrence of Ru,Si, was not confirmed. (C) 1999 Elsevier Science S.A. All rights reserved.

Superior flow for bridge to life with self-expanding venous cannulas.

BACKGROUND: Recently, a compact cardiopulmonary support (CPS) system designed for quick set-up for example, during emergency cannulation, has been introduced. Traditional rectilinear percutaneous cannulas are standard for remote vascular access with the original design. The present study was designed to assess the potential of performance increase by the introduction of next-generation, self-expanding venous cannulas, which can take advantage of the luminal width of the venous vasculature despite a relatively small access orifice. METHODS: Veno-arterial bypass was established in three bovine experiments (69+/-10 kg). The Lifebridge (Lifebridge GmbH, Munich, Germany) system was connected to the right atrium in a trans-jugular fashion with various venous cannulas; and the oxygenated blood was returned through the carotid artery with a 17 F percutaneous cannula. Two different venous cannulas were studied, and the correlation between the centrifugal pump speed (1500-3900 RPM), flow and the required negative pressure on the venous side was established: (A) Biomedicus 19 F (Medtronic, Tolochenaz, Switzerland); (B) Smart canula 18 F/36 F (Smartcanula LLC, Lausanne, Switzerland). RESULTS: At 1500 RPM, the blood flow was 0.44+/-0.26 l min(-1) for the 19 F rectilinear cannula versus 0.73+/-0.34 l min(-1) for the 18/36 F self-expanding cannula. At 2500 RPM the blood flow was 1.63+/-0.62 l min(-1) for the 19F rectilinear cannula versus 2.13+/-0.34 l min(-1) for the 18/36 F self-expanding cannula. At 3500 RPM, the blood flow was 2.78+/-0.47 l min(-1) for the 19 F rectilinear cannula versus 3.64+/-0.39 l min(-1) for the 18/36 F self-expanding cannula (p<0.01 for 18/36 F vs 19 F). At 1500 RPM, the venous line pressure was 18+/-8 mmHg for the 19F rectilinear cannula versus 19+/-5 mmHg for the 18/36 F self-expanding cannula. At 2500 RPM the venous line pressure accounted for -22+/-32 mmHg for the 19 F rectilinear cannula versus 2+/-5 mmHg for the 18/36 F self-expanding cannula. At 3500 RPM, the venous line pressure was -112+/-42 mmHg for the rectilinear cannula versus 28+/-7 mmHg for the 18/36 F self-expanding cannula (p<0.01 for 18 F/36 F vs 19 F). Conclusions: The negative pressure required to achieve adequate venous drainage with the self-expanding venous cannula accounts for approximately 31% of the pressure necessary with the 19 F rectilinear cannula. In addition, a pump flow of more than 4 l min(-1) can be achieved with the self-expanding design and a well-accepted negative inlet pressure for minimal blood trauma of less than 50 mmHg.

Long-term continuous-flow left ventricular assist devices (LVAD) as bridge to heart transplantation.

Heart transplantation (HTx) is the treatment of choice for end-stage heart failure but the limited availability of heart's donors still represents a major issue. So long-term mechanical circulatory support (MCS) has been proposed as an alternative treatment option to assist patients scheduled on HTx waiting list bridging them for a variable time period to cardiac transplantation-the so-called bridge-to-transplantation (BTT) strategy. Nowadays approximately 90% of patients being considered for MCS receive a left ventricular assist device (LVAD). In fact, LVAD experienced several improvements in the last decade and the predominance of continuous-flow over pulsatile-flow technology has been evident since 2008. The aim of the present report is to give an overview of continuous-flow LVAD utilization in the specific setting of the BTT strategy taking into consideration the most representative articles of the scientific literature and focusing the attention on the evolution, clinical outcomes, relevant implications on the HTx strategy and future perspectives of the continuous-flow LVAD technology.

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014.

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma.