Comprehensive characterization of molecular interactions based on nanomechanics

Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6) Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions

Identifying the prevalence of Parkinson's disease in Denmark using healthcare registries and self-reported survey data

INTRODUCTION: Existing estimates of PD prevalence in Denmark are lower than those in the rest of Europe and are based on identification via single registries. Hence, are aim was to use a combined registry/self-report survey approach to identify people with PD and also investigate whether using different registry methods led to differences in the accuracy, completeness and characteristics of the identified cohorts.METHODS: This study had a cross-sectional design using routinely collected health registry data to identify adults, ≥18 years of age and resident in Denmark, with PD from either the Danish National Patient (DNP) registry or Danish Prescription Medicines (DPM) registry. Those identified were asked to confirm their PD diagnosis using a national self-report survey.RESULTS: 13,433 people were identified potentially as having PD via the DNP or DPM registry and sent a survey. Of these, 9094 responded (68 %) of which 85 % confirmed they had PD (n = 7763; 194/100,000; 95%CI:7650-7876). When adjusting for non-respondents, assuming an equal rate of confirmation in respondents and non-respondents, estimated Danish PD population was 11,467 (198.4/100,000; 95 % CI:197.2-199.6). Identification of people using those found in both registries led to 98 % confirming they had PD versus using one registry: DNP 93 % and DPM 88 %. No clear differences in sociodemographic characteristics were found between different registry identification methods.CONCLUSIONS: Estimated PD population in Denmark was significantly higher than previous Danish estimates and close to existing estimates in other European countries. The most accurate PD population was identified when including those found in both the DNP and DPM registries.</p

I Tensed the Laws and the Laws Won: Non-Eternalist Humeanism

ABSTRACT In this paper, I propose a variant of a Humean account of laws called "Open Future Humeanism" (OFH), which holds that since the laws supervene partly on future events, there are at any instant infinitely many possible future courses of events. I argue that if one wants to take the openness of the future that OFH proposes ontologically serious, then OFH is best represented within a growing block view of time. I further discuss some of OFH's problems which stem from the fact that in this view, there are no laws as long as time progresses. These problems can be solved by adding a temporal operator to the laws, so that at any instant, we get a set of tensed laws which held up to and including that instant