A Multi-Channel Vital Signal Processing Method for Detection and Validation of Respiration Disorders

This paper presents a method for the detection and reliable validation of respiration disorder by using multi-channel vital signal processing. The main scope is the automated detection and analysis of a very common respiration disorder, the apnea syndrome. Apnea diagnostics requires long-term multi-channel vital signal recording, called polygraphy. Although various methods already exist for the computer-aided analysis of polygrams, only some of them offer precise apnea typing (i.e. distinguish between central vs. obstructive episodes) and event validation. The system introduced in this paper processes respiration, heart rate, blood pressure, and blood oxygen saturation signals. The episodes of apnea are classified, typed and validated over an 80\% success rate compared to reference annotations made by medical experts. The detected episodes are validated by the rule-based classification of the characteristic changes in the cardiovascular signals caused by episodes of apnea

PEAR, a flexible fluorescent reporter for the identification and enrichment of successfully prime edited cells

Prime editing is a recently developed CRISPR/Cas9 based gene engineering tool that allows the introduction of short insertions, deletions, and substitutions into the genome. However, the efficiency of prime editing, which typically achieves editing rates of around 10%-30%, has not matched its versatility. Here, we introduce the prime editor activity reporter (PEAR), a sensitive fluorescent tool for identifying single cells with prime editing activity. PEAR has no background fluorescence and specifically indicates prime editing events. Its design provides apparently unlimited flexibility for sequence variation along the entire length of the spacer sequence, making it uniquely suited for systematic investigation of sequence features that influence prime editing activity. The use of PEAR as an enrichment marker for prime editing can increase the edited population by up to 84%, thus significantly improving the applicability of prime editing for basic research and biotechnological applications

Biológiai jelek információjának diagnosztikai célú kutatása rendszerelméleti megközelítéssel = System theory approach of the information of the biological signals for diagnostics

Kidolgoztunk egy új magzati fonokardiográfiás mérési és jelfeldolgozási módszert az FHR hosszú távú robusztus meghatározására. Létrehoztunk egy neurális hálzatokat alkalmazó légzési rendellenesség felismerő rendszert. Megalkottuk számos, a csecsemősírás jellemzésére szolgáló paraméter meghatározásának módszerét, és összehasonlítottuk több száz csecsemő sírását e paraméterek alapján. Több betegségcsoportnál jellemző eltéréseket tapasztaltunk. Neurolingvisztikai kutatásunk során megvalósítottunk egy lingvisztikai adatbázis-struktúrát és a hozzá tartozó adatbázis-kezelő segédprogramot. Nyelvi adatbázisunk struktúráját kiterjesztettük, valamint megvalósítottunk néhány új algoritmust, melyek lehetővé teszik a terápiás gyakorlatok során magasabb nyelvi modalitások felhasználását is. | We've worked out a novel vital phonocardiographic measurement ad signal processing method to determine robustly the longterm fetal heart rate (FHR). We'v created system to recognize respiration disorders containing a neural network. We developed new algorithms and methods in the analysis of the infant cry to check disorders during infancy. We analysed the crying sound from hundreds of infanst and found differences between healthy and unhealthy infants. In our neurolinguistic research we created a novel computer-aided training and rehabilitaion approach to the therapy of aphasia. The system helps to treat and overcome the most severe consequences of this language disorder. The developed system is embedded into a tele-rehabilitation framework, which offers a uniform interface for various telecare applications

A Genetically Encoded Isonitrile Lysine for Orthogonal Bioorthogonal Labeling Schemes

Bioorthogonal click-reactions represent ideal means for labeling biomolecules selectively and specifically with suitable small synthetic dyes. Genetic code expansion (GCE) technology enables efficient site-selective installation of bioorthogonal handles onto proteins of interest (POIs). Incorporation of bioorthogonalized non-canonical amino acids is a minimally perturbing means of enabling the study of proteins in their native environment. The growing demand for the multiple modification of POIs has triggered the quest for developing orthogonal bioorthogonal reactions that allow simultaneous modification of biomolecules. The recently reported bioorthogonal [4 + 1] cycloaddition reaction of bulky tetrazines and sterically demanding isonitriles has prompted us to develop a non-canonical amino acid (ncAA) bearing a suitable isonitrile function. Herein we disclose the synthesis and genetic incorporation of this ncAA together with studies aiming at assessing the mutual orthogonality between its reaction with bulky tetrazines and the inverse electron demand Diels–Alder (IEDDA) reaction of bicyclononyne (BCN) and tetrazine. Results showed that the new ncAA, bulky-isonitrile-carbamate-lysine (BICK) is efficiently and specifically incorporated into proteins by genetic code expansion, and despite the slow [4 + 1] cycloaddition, enables the labeling of outer membrane receptors such as insulin receptor (IR) with a membrane-impermeable dye. Furthermore, double labeling of protein structures in live and fixed mammalian cells was achieved using the mutually orthogonal bioorthogonal IEDDA and [4 + 1] cycloaddition reaction pair, by introducing BICK through GCE and BCN through a HaloTag technique

Effective Synthesis, Development and Application of a Highly Fluorescent Cyanine Dye for Antibody Conjugation and Microscopy Imaging

An asymmetric cyanine-type fluorescent dye was designed and synthesized via a versatile, multi-step process, aiming to conjugate with an Her2+ receptor specific antibody by an azide-alkyne click reaction. The aromaticity and the excitation and relaxation energetics of the fluorophore were characterized by computational methods. The synthesized dye exhibited excellent fluorescence properties for confocal microscopy, offering efficient applicability in in vitro imaging due to its merits such as a high molar absorption coefficient (36 816 M-1 cm-1), excellent brightness, optimal wavelength (627 nm), larger Stokes shift (26 nm) and appropriate photostability compared to cyanines. The conjugated cyanine-trastuzumab was constructed via an effective, metal-free, strain-promoted azide-alkyne click reaction leading to a regulated number of dyes being conjugated. This novel cyanine-labelled antibody was successfully applied for in vitro confocal imaging and flow cytometry of Her2+ tumor cells