Quantum-secured time transfer between precise timing facilities: a field trial with simulated satellite links

Global Navigation Satellite Systems (GNSSs), such as GPS and Galileo, provide precise time and space coordinates globally and constitute part of the critical infrastructure of modern society. To reliably operate GNSS, a highly accurate and stable system time is required, such as the one provided by several independent clocks hosted in Precise Timing Facilities (PTFs) around the world. The relative clock offset between PTFs is periodically measured to have a fallback system to synchronize the GNSS satellite clocks. The security and integrity of the communication between PTFs is of paramount importance: if compromised, it could lead to disruptions to the GNSS service. Therefore, securing the communication between PTFs is a compelling use-case for protection via Quantum Key Distribution (QKD), since this technology provides information-theoretic security. We have performed a field trial demonstration of such a use-case by sharing encrypted time synchronization information between two PTFs, one located in Oberpfaffenhofen (Germany) and one in Matera (Italy)—more than 900 km apart. To bridge this large distance, a satellite-QKD system is required, plus a “last-mile” terrestrial link to connect the optical ground station (OGS) to the actual location of the PTF. In our demonstration, we have deployed two full QKD systems to protect the last-mile connection at both locations and have shown via simulation that upcoming QKD satellites will be able to distribute keys between Oberpfaffenhofen and Matera, exploiting already existing OGSs

Flexible biochips for detection of biomolecules

Miniaturization of biosensors is envisaged by the development of biochips consisting of parallel microarray patterns of binding sites on rigid substrates, such as glass or silicon. Thin plastic substrates are promising flexible alternatives because of the possibility for large-area roll-to-roll manufacturing of disposable chips at lower costs. Mature optical lithography technology faces many challenges when used to pattern flexible foils as a result of the substrate instabilities, especially at higher temperatures. In this work, flexible biochips with gold electrode patterns were fabricated on thin polyethylene naphthalate (PEN) foils using photolithography. The gold electrode structures of the chips were manufactured by direct metal patterning and by lift-off processing. Both methodologies resulted in well-defined electrode patterns as concluded from optical microscopy and scanning electron microscopy (SEM) characterization and resistance measurements. The biochips were successfully employed for the electrical and optical detection of DNA molecules. The DNA detection was based on the immobilization of capture DNA between electrode gaps, hybridization with biotin-labeled target DNA, and enzymatic silver enhancement. © 2009 American Chemical Society

Organic RFID transponder chip with data rate compatible with electronic product coding

Data rates of plastic transponder chips have been limited to a few kHz, limited by the inherent low mobility of organic semiconductors. However, a target application for plastic RFID tags is Electronic Product Coding (EPC), which will require, at a base carrier frequency fc = 13.56 MHz, a data rate of fc/512 = 52.969 kb/s. In this work, we show that the compatibility of organic semiconductors with high-k gate dielectrics allows boosting the current drive of transistors in functional circuits to EPC compatible clock rates. We demonstrate an 8 bit RFID transponder chip with critical dimension of 2 lm having a data rate of 50 kb/s at VDD = 18 V. © 2010 Elsevier B.V. All rights reserved

Thin-film transistors and circuits on plastic foil

We present our recent achievements in organic semiconductor technology in two emerging application areas. We show that the performance of our technology approaches the requirements for Electronic Product Coding RFID tags. Also, backplanes of OLED displays are enabled by the unique compatibility of pentacene transistors with high-k gate dielectrics. © 2009 IEEE

Whole exome sequencing in 342 congenital cardiac left sided lesion cases reveals extensive genetic heterogeneity and complex inheritance patterns

Abstract Background Left-sided lesions (LSLs) account for an important fraction of severe congenital cardiovascular malformations (CVMs). The genetic contributions to LSLs are complex, and the mutations that cause these malformations span several diverse biological signaling pathways: TGFB, NOTCH, SHH, and more. Here, we use whole exome sequence data generated in 342 LSL cases to identify likely damaging variants in putative candidate CVM genes. Methods Using a series of bioinformatics filters, we focused on genes harboring population-rare, putative loss-of-function (LOF), and predicted damaging variants in 1760 CVM candidate genes constructed a priori from the literature and model organism databases. Gene variants that were not observed in a comparably sequenced control dataset of 5492 samples without severe CVM were then subjected to targeted validation in cases and parents. Whole exome sequencing data from 4593 individuals referred for clinical sequencing were used to bolster evidence for the role of candidate genes in CVMs and LSLs. Results Our analyses revealed 28 candidate variants in 27 genes, including 17 genes not previously associated with a human CVM disorder, and revealed diverse patterns of inheritance among LOF carriers, including 9 confirmed de novo variants in both novel and newly described human CVM candidate genes (ACVR1, JARID2, NR2F2, PLRG1, SMURF1) as well as established syndromic CVM genes (KMT2D, NF1, TBX20, ZEB2). We also identified two genes (DNAH5, OFD1) with evidence of recessive and hemizygous inheritance patterns, respectively. Within our clinical cohort, we also observed heterozygous LOF variants in JARID2 and SMAD1 in individuals with cardiac phenotypes, and collectively, carriers of LOF variants in our candidate genes had a four times higher odds of having CVM (odds ratio = 4.0, 95% confidence interval 2.5–6.5). Conclusions Our analytical strategy highlights the utility of bioinformatic resources, including human disease records and model organism phenotyping, in novel gene discovery for rare human disease. The results underscore the extensive genetic heterogeneity underlying non-syndromic LSLs, and posit potential novel candidate genes and complex modes of inheritance in this important group of birth defects

Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations

Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFN. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations (1.4%) in 77 genes (13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate