Interplay between CFTR Phosphorylation, CFTR-ATPase Activity, and Anion Flux

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR, ABCC7), mutations of which cause CF, belongs to the ATP binding cassette (ABC) transporter family and works as a channel for small anions, such as chloride and bicarbonate. Anion channel activity is known to depend on phosphorylation by cAMP-dependent protein kinase A (PKA) and CFTR-ATPase activity. Whereas anion channel activity has been extensively investigated, phosphorylation and CFTR-ATPase activity are still poorly understood. Here, we show that the two processes can be measured in a label-free and non-invasive manner in real time in live cells, stably transfected with CFTR. This study reveals three key findings. (i) The major contribution to the total CFTR-related ATP hydrolysis rate (≥ 90 %) is due to phosphorylation by PKA and the minor contribution (≤ 10 %) to CFTR-ATPase activity. (ii) The mutant CFTR-E1371S which is still conductive, but defective in ATP hydrolysis, is not phosphorylated, suggesting that phosphorylation requires a functional nucleotide binding domain and occurs in the post-hydrolysis transition state. (iii) CFTR-ATPase activity is inversely related to CFTR anion flux. The present data are consistent with a model in which CFTR is in a closed conformation with two ATPs bound. The open conformation is induced by ATP hydrolysis and corresponds to the post hydrolysis transition state which is stabilized by phosphorylation and binding of chloride channel potentiators

Predicting Disease-Gene Associations using Cross-Document Graph-based Features

ter Horst H, Hartung M, Klinger R, Zwick M, Cimiano P. Predicting Disease-Gene Associations using Cross-Document Graph-based Features. Bielefeld: Bielefeld University; 2016.In the context of personalized medicine, text mining methods pose an interesting option for identifying disease-gene associations, as they can be used to generate novel links between diseases and genes which may complement knowledge from structured databases. The most straightforward approach to extract such links from text is to rely on a simple assumption postulating an association between all genes and diseases that co-occur within the same document. However, this approach (i) tends to yield a number of spurious associations, (ii) does not capture different relevant types of associations, and (iii) is incapable of aggregating knowledge that is spread across documents. Thus, we propose an approach in which disease-gene co-occurrences and gene-gene interactions are represented in an RDF graph. A machine learning-based classifier is trained that incorporates features extracted from the graph to separate disease-gene pairs into valid disease-gene associations and spurious ones. On the manually curated Genetic Testing Registry, our approach yields a 30 points increase in F 1 score over a plain co-occurrence baseline

Gain enhancement of BiCMOS on-chip sub-THz antennas by mean of meta-cells

A MM-loaded sub-THz on-chip antenna with a narrow beamwidth, 9 dB gain and a simulated peak efficiency of 76% at the center frequency of 300 GHz is presented. By surrounding the antenna with a single MM-cell ring defined solely on the top metal of the back-end of line, an efficient suppression of the surface waves is obtained. The on-chip antenna has been designed using IHPs 130 nm SiGe BiCMOS technology with a 7-layer metallization stack, combined with the local backside etching process aimed to creating an air cavity which is then terminated by a reflective plane. By comparing the measured MM-loaded antenna performances to its non-MM-loaded counterpart, an enhanced integrity of the main lobe due to the MM-cells shielding effect can be observed. An excellent agreement between the simulated and measured performances has been found, which makes the MM-loaded antennas a valid alternative for the upcoming next-generation sub-THz transceivers

Letter: A Note on Neurosurgical Resection and Why We Need to Rethink Cutting

Peer Reviewe

Молодежь и современные информационные технологии: сборник трудов XVI Международной научно-практической конференции студентов, аспирантов и молодых учёных, 3-7 декабря 2018 г., г. Томск

Сборник содержит доклады, представленные на XVI Международной научно-практической конференции студентов, аспирантов и молодых ученых «Молодежь и современные информационные технологии», прошедшей в Томском политехническом университете на базе Инженерной школы информационных технологий и робототехники. Материалы сборника отражают доклады студентов, аспирантов и молодых ученых, принятые к обсуждению на секциях: «Компьютерное моделирование и интеллектуальный анализ данных», «Автоматизация и управление в технических системах», «Робототехнические и мехатронные системы», «Цифровизация, IT и цифровая экономика», «Компьютерная графика и дизайн». Сборник предназначен для специалистов в области информационных технологий, студентов и аспирантов соответствующих специальностей

Transcriptomic characterization of culture-associated changes in murine and human precision-cut tissue slices

Our knowledge of complex pathological mechanisms underlying organ fibrosis is predominantly derived from animal studies. However, relevance of animal models for human disease is limited; therefore, an ex vivo model of human precision-cut tissue slices (PCTS) might become an indispensable tool in fibrosis research and drug development by bridging the animal-human translational gap. This study, presented as two parts, provides comprehensive characterization of the dynamic transcriptional changes in PCTS during culture by RNA sequencing. Part I investigates the differences in culture-induced responses in murine and human PCTS derived from healthy liver, kidney and gut. Part II delineates the molecular processes in cultured human PCTS generated from diseased liver, kidney and ileum. We demonstrated that culture was associated with extensive transcriptional changes and impacted PCTS in a universal way across the organs and two species by triggering an inflammatory response and fibrosis-related extracellular matrix (ECM) remodelling. All PCTS shared mRNA upregulation of IL-11 and ECM-degrading enzymes MMP3 and MMP10. Slice preparation and culturing activated numerous pathways across all PCTS, especially those involved in inflammation (IL-6, IL-8 and HMGB1 signalling) and tissue remodelling (osteoarthritis pathway and integrin signalling). Despite the converging effects of culture, PCTS display species-, organ- and pathology-specific differences in the regulation of genes and canonical pathways. The underlying pathology in human diseased PCTS endures and influences biological processes like cytokine release. Our study reinforces the use of PCTS as an ex vivo fibrosis model and supports future studies towards its validation as a preclinical tool for drug development

Wireless THz link with optoelectronic transmitter and receiver

Photonics might play a key role in future wireless communication systems that operate at terahertz (THz) carrier frequencies. A prime example is the generation of THz data streams by mixing optical signals in high-speed photodetectors. Over previous years, this concept has enabled a series of wireless transmission experiments at record-high data rates. Reception of THz signals in these experiments, however, still relied on electronic circuits. In this paper, we show that wireless THz receivers can also greatly benefit from optoelectronic signal processing techniques, in particular when carrier frequencies beyond 0.1 THz and wideband tunability over more than an octave is required. Our approach relies on a high-speed photoconductor and a photonic local oscillator for optoelectronic downconversion of THz data signals to an intermediate frequency band that is easily accessible by conventional microelectronics. By tuning the frequency of the photonic local oscillator, we can cover a wide range of carrier frequencies between 0.03 and 0.34 THz. We demonstrate line rates of up to 10 Gbit/s on a single channel and up to 30 Gbit/s on multiple channels transmitted over a distance of 58 m. To the best of our knowledge, our experiments represent the first demonstration of a THz communication link that exploits optoelectronic signal processing techniques both at the transmitter and the receiver

Wireless THz link with optoelectronic transmitter and receiver

Photonics might play a key role in future wireless communication systems that operate at terahertz (THz) carrier frequencies. A prime example is the generation of THz data streams by mixing optical signals in high-speed photodetectors. Over previous years, this concept has enabled a series of wireless transmission experiments at record-high data rates. Reception of THz signals in these experiments, however, still relied on electronic circuits. In this paper, we show that wireless THz receivers can also greatly benefit from optoelectronic signal processing techniques, in particular when carrier frequencies beyond 0.1 THz and wideband tunability over more than an octave is required. Our approach relies on a high-speed photoconductor and a photonic local oscillator for optoelectronic downconversion of THz data signals to an intermediate frequency band that is easily accessible by conventional microelectronics. By tuning the frequency of the photonic local oscillator, we can cover a wide range of carrier frequencies between 0.03 and 0.34 THz. We demonstrate line rates of up to 10 Gbit/s on a single channel and up to 30 Gbit/s on multiple channels transmitted over a distance of 58 m. To the best of our knowledge, our experiments represent the first demonstration of a THz communication link that exploits optoelectronic signal processing techniques both at the transmitter and the receiver

Design and Integration of a Multi-arm Installation Robot Demonstrator for orbital large Assembly

Space facilities for orbital exploitation and exploration missions are increasingly requiring larger structure to extend their capabilities. Dimensions of future scientific outposts, solar stations and telescopes undoubtedly matter to expand our horizons, power our planet or explore the universe. Due to the foreseen large structures for such applications, a single self-deploying piece contained in standard launcher fairings might become inadequate. Another approach is that large structures could be broken down into standard modules that will be built in-orbit. Assembling large structure in space is particularly challenging but the raise of key enablers as standard interconnects and advanced robotics opens a new horizon for such applications. It is assumed here that the large spacecraft structure and modules are equipped with standard interconnects (SI) that allow them to be mated to each other and to the robot system for manipulation/transport/installation, or to allow the robot system to move across them. This paper introduces the concept of a novel Multi-Arm Robot (MAR) dedicated to on-orbit large telescope assembly, its ground equivalent laboratory demonstrator design and preliminary hardware integration. The MAR is a modular robot composed of three robotic subsystems - a torso and two symmetrical 7-degree of freedom (DOF) anthropomorphic arms with non-spherical wrists - that are functionally independent and can be connected by the means of Standard Interconnects. The modular approach of the MAR reduces the complexity of the different robotic appendages and offers a set of robotic configuration that extends the range of possible operations and provides an intrinsic system redundancy that reduces the overall mission risk. To assess the MAR concept, a Technology Readiness Level (TRL) 4 ground demonstrator, has been designed to provide a framework that allows the multi-arm robot to execute its overall scope of operations in a ground laboratory environment. It comprises a testbed (dummy spacecraft structure, home base, storage area and mobile payloads) offering a space representative environment, a mission control center (computer, simulator and electrical/data support equipment) supervising the MAR's tasks, and a gravity compensation system (gantry crane and offloading system) for supporting the robot under 1-g