University of Groningen

About: University of Groningen is a education organization based out in Groningen, Groningen, Netherlands. It is known for research contribution in the topics: Population & Context (language use). The organization has 36346 authors who have published 69116 publications receiving 2940370 citations. The organization is also known as: Rijksuniversiteit Groningen & RUG.

Electrical spin injection and accumulation at room temperature in an all-metal mesoscopic spin valve

Abstract: Finding a means to generate, control and use spin-polarized currents represents an important challenge for spin-based electronics, or `spintronics'. Spin currents and the associated phenomenon of spin accumulation can be realized by driving a current from a ferromagnetic electrode into a non-magnetic metal or semiconductor. This was first demonstrated over 15 years ago in a spin injection experiment on a single crystal aluminium bar at temperatures below 77 K. Recent experiments have demonstrated successful optical detection of spin injection in semiconductors, using either optical injection by circularly polarized light or electrical injection from a magnetic semiconductor. However, it has not been possible to achieve fully electrical spin injection and detection at room temperature. Here we report room-temperature electrical injection and detection of spin currents and observe spin accumulation in an all-metal lateral mesoscopic spin valve, where ferromagnetic electrodes are used to drive a spin-polarized current into crossed copper strips. We anticipate that larger signals should be obtainable by optimizing the choice of materials and device geometry.

Frequent and Focal FGFR1 Amplification Associates with Therapeutically Tractable FGFR1 Dependency in Squamous Cell Lung Cancer

Abstract: Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1(V561M)), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.

How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Abstract: Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the 'HFA-PEFF diagnostic algorithm'. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for heart failure symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular (LV) ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e'), LV filling pressure estimated using E/e', left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2-4 points) implies diagnostic uncertainty, in which case Step 3 (F1 : Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2 : Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.