A high-Tc 4-bit periodic threshold analog-to-digital converter

Using ramp-type Josephson junctions a 4-bit periodic threshold ADC has been designed, fabricated and tested. Practical design constraints will be discussed in terms of noise immunity, flux flow, available technology, switching speed etc. In a period of four years we fabricated about 100 chips in order to bring the technology to an acceptable level and to test various designs and circuit layouts. This resulted in a basic comparator that is rather insensitive to the stray field generated by the analog input signal or variations in mask alignment during fabrication. The input signal is fed into the comparators using a resistive divider network. Full functionality at low frequencies has been demonstrate

The Remains of the Night

Several theories claim that the rhythms of daily life changed dramatically in the late eighteenth century, as a result of the advent of street lighting. New technologies made it possible to work longer hours, enjoy a dash of leisure time, or otherwise stay active during the evening. People thus slowly but surely ‘colonized’ the night. Drawing on new empirical data from the eyewitness accounts of the local criminal court in Antwerp, this article subjects this theory to a thorough investigation. The findings show that there was no real increase in nocturnalization because Antwerpers – even without new street lamps – remained active for a long time anyway. They usually continued working long after sunset or had time for leisure. Sleep was limited to the biological minimum. A deviant rhythm in which people remained active until the wee hours of the morning and only got up well after sunrise was reserved for a small group of people who belonged either to the absolute cream of the crop or to the fringes of society

An HTS Quasi-One junction SQUID-based periodic threshold comparator for a 4-bit superconductive flash A/D converter

An all high-Tc periodic threshold comparator for application in a 4-bit superconductive A/D converter has been realized and tested. The theoretical threshold curve of the comparator is calculated and compared to the measured results. Furthermore, the thermal noise immunity and the influence of flux-flow are considered, resulting in practical design constraints for the comparator circui

Review of periodical articles

Historians are held hostage by the sources that are available to them, and for that reason, the historiography of medieval towns is dominated by research on thirteenth-, fourteenth- or fifteenth-century case-studies. In preceding centuries, literacy was largely the monopoly of ecclesiastical milieus, who were often hostile or simply not interested in describing the urban settlements which then emerged all over Europe. An interesting exception, however, is the Breton town of Redon, which took shape around an abbey that was established in 832 with support of the Carolingian Emperor Louis the Pious. By navigating the unusually extensive set of Carolingian cartularies of this abbey, as well as the available cartographic and archaeological evidence, Julien Bachelier has developed an incisive sketch of the development of a town in the shadow of the Carolingian abbey in the eleventh and twelfth centuries (‘Une ville abbatiale bretonne. Redon du IXe au XIVe siècle’, Histoire Urbaine, 48 (2017), 133–54). This case-study confirms once again that the urbanization of medieval Europe was more than a side-effect of the rebirth of long-distance trade as the canonical Pirenne thesis would have it. The Redon case provides a valuable contribution to the revisionist perspective that stresses the importance of local demand from abbeys, episcopal palaces and castles as a stimulus for urban development (see esp. the seminal work of A. Verhulst, The Rise of Cities in North-West Europe (Cambridge, 1999))

Diagnostic Gene Panel Testing in (Non)-Syndromic Patients with Cleft Lip, Alveolus and/or Palate in the Netherlands

Objectives: Clefts of the lip, alveolus and/or palate (CLA/P) are the most common craniofacial congenital malformations in humans. These oral clefts can be divided into non-syndromic (isolated) and syndromic forms. Many cleft-related syndromes are clinically variable and genetically heterogeneous, making it challenging to distinguish syndromic from non-syndromic cases. Recognition of syndromic/genetic causes is important for personalized tailored care, identification of (unrecognized) comorbidities, and accurate genetic counseling. Therefore, next generation sequencing (NGS)-based targeted gene panel testing is increasingly implemented in diagnostics of CLA/P patients. In this retrospective study, we assess the yield of NGS gene panel testing in a cohort of CLA/P cases.Methods: Whole exome sequencing (WES) followed by variant detection and interpretation in an a priori selected set of genes associated with CLA/P phenotypes was performed in 212 unrelated CLA/P patients after genetic counseling between 2015 and 2020. Medical records including family history and results of additional genetic tests were evaluated.Results: In 24 CLA/P cases (11.3%), a pathogenic genetic variant was identified. Twenty out of these 24 had a genetic syndrome requiring specific monitoring and follow-up. Six of these 24 cases (25%) were presumed to be isolated CLA/P cases prior to testing, corresponding to 2.8% of the total cohort. In eight CLA/P cases (3.8%) without a diagnosis after NGS-based gene panel testing, a molecular diagnosis was established by additional genetic analyses (e.g., SNP array, single gene testing, trio WES).Conclusion: This study illustrates NGS-based gene panel testing is a powerful diagnostic tool in the diagnostic workup of CLA/P patients. Also, in apparently isolated cases and non-familial cases, a genetic diagnosis can be identified. Early diagnosis facilitates personalized care for patients and accurate genetic counseling of their families.</p

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and