Cross-Bridge Kelvin resistor structures for reliable measurement of low contact resistances and contact interface characterization

The parasitic factors that strongly influence the measurement accuracy of Cross-Bridge Kelvin Resistor (CBKR) structures for low specific contact resistances (rhoc) have been extensively discussed during last few decades and the minimum of the rhoc value, which could be accurately extracted, was estimated. We fabricated a set of various metal-to-metal CBKR structures with different geometries, i.e., shapes and dimensions, to confirm this limit experimentally and to create a method for contact metal-to-metal interface characterization. As a result, a model was developed to account for the actual current flow and a method for reliable rhoc extraction was created. This method allowed to characterize metal-to-metal contact interface. It was found that in the case of ideal metal-to-metal contacts, the measured CBKR contact resistance was determined by the dimensions of the two-metal stack in the area of contact and sheet resistances of the metals used

A 107GHz LNA in 65nm CMOS with inductive neutralization and slow-wave transmission lines

This paper presents a 107GHz LNA prototype using TSMC 65nm CMOS technology. It explores the limit of the CMOS technology by effectively optimizing the active and passive devices. An improvement of 1.6dB higher maximum stable/available gain (MSG/MAG) on the transistor is achieved around 110GHz by layout optimization and inductor neutralization technique. A high quality factor co-planar waveguide (CPW) transmission line is designed utilizing the slow-wave effect. A quality factor of 23.6 is demonstrated by EM-simulations while taken the consideration of satisfying the stringent layout design rules. Based on the optimization on the active and passive devices, a dual-stage LNA is designed, with a simulated power gain of 10.2dB and noise figure of 8dB at 107GHz, verified by chip-level EM-simulations. The power consumption is 28.2mW

Bridging the gap between clinical trials and real-world for advanced melanoma: Results of the Dutch Melanoma Treatment Registry

In this dissertation, new immune and targeted therapies for advanced melanoma were investigated in daily practice in the Netherlands.From 2013 to 2017, new treatments were implemented fast and save with an increase of median survival. Increased LDH, distance metastases in ≥3 organsites, brain and liver metastases and ECOG performance score were associated with death. Survival of advanced mucosal melanoma lagged behind. Forty percent of patients receiving systemic treatment did not meet ≥1 selection criteria of clinical trials. In these patients, LDH was the most important prognostic factor, followed by the ECOG performance score and brain metastases. For anti-PD-1 antibody monotherapy, a median survival of 24 months was observed. A complete response or a shorter time to the first response were associated with disease controle when anti-PD-1 montherapy was discontinued in the absence of progression. Half of the patients treated with anti-CTLA-4 plus anti-PD-1 antibodies had a grade 3-4 adverse event, requiering hospital admission in 50%. On the other hand, 37% of patients reached disease control after 2 years, with a median survival of 28.7 months. This dissertation emphasizes that with new treatments there is an "knowledge-gap" between the clinical trials and real-world that should be bridged with real-world data.LUMC / Geneeskund

Close the Gap : a study on the regulation of Connexin43 gap junctional communication

Gap junctions are groups of transmembrane channels that connect the cytoplasms of adjacent cells to mediate the diffusion of small molecules, such as ions, metabolites, second messengers and small peptides. The building blocks of gap junctions are connexin proteins. The most ubiquitous and best studied connexin is connexin43 (Cx43). Cx43 is also known as the heart connexin. In the heart, gap junctional communication between cardiomyocytes ensures efficient electrical coupling and hence the synchronous propagation of action potentials. Misregulation of Cx43 expression, localisation and channel gating may lead to severe cardiac dysfunction. Cx43-based cell-cell coupling is rapidly disrupted following stimulation of certain G protein-coupled receptors (GPCRs). The studies presented in this thesis focus on the quest to unravel the signalling pathways leading to the transient inhibition of Cx43-based communication by GPCR activation. Our results suggest a model in which GPCR agonists inhibit Cx43-based gap junctional communication in two phases. Initial closure of the Cx43 channels si mediated by depletion of the phospholipid PIP2 from the plasma membrane, followed by internalisation of the gap junctions due to ubiquitination of Cx43 by the ubiquitin ligase Nedd4. New insights into the mechanisms underlying Cx43 gap junction closure may lead to new treatments of heart failure.KWF CBGUBL - phd migration 201