Interpretable detection of novel human viruses from genome sequencing data

Viruses evolve extremely quickly, so reliable meth- ods for viral host prediction are necessary to safe- guard biosecurity and biosafety alike. Novel human- infecting viruses are difficult to detect with stan- dard bioinformatics workflows. Here, we predict whether a virus can infect humans directly from next- generation sequencing reads. We show that deep neural architectures significantly outperform both shallow machine learning and standard, homology- based algorithms, cutting the error rates in half and generalizing to taxonomic units distant from those presented during training. Further, we develop a suite of interpretability tools and show that it can be applied also to other models beyond the host pre- diction task. We propose a new approach for con- volutional filter visualization to disentangle the in- formation content of each nucleotide from its contri- bution to the final classification decision. Nucleotide- resolution maps of the learned associations between pathogen genomes and the infectious phenotype can be used to detect regions of interest in novel agents, for example, the SARS-CoV-2 coronavirus, unknown before it caused a COVID-19 pandemic in 2020. All methods presented here are implemented as easy- to-install packages not only enabling analysis of NGS datasets without requiring any deep learning skills, but also allowing advanced users to easily train and explain new models for genomics.Peer Reviewe

Konzeption und Entwicklung eines auf DeepSpeech basierenden Open Source Editors zur Transkription von Audio- und Videomaterial

More and more often, spoken information must and should be available in written form. For this purpose, various transcription programs try to support the user with various conveniences when transcribing the source material. A variety of online services go one step further and provide a ready-to-use, automatically generated transcription for a fee. Since the fees can be very expensive for the individual user and the online services may not always be used for privacy reasons, the goal of this work is to implement an open offline alternative. This alternative should be an open source editor based on the open speech-to-text-engine DeepSpeech and should on one hand provide the user with an offline transcription and on the other hand support him in correcting it. To achieve this goal, first the traditional speech recognition and eventually DeepSpeech will be described. This is followed by the conception and implementation of the editor. Since this project is explicitly intended to be an open source project, the last part will take a closer look at the release

Asymmetric copper-catalyzed C-N cross-couplings induced by visible light

Despite a well-developed and growing body of work in copper catalysis, the potential of copper to serve as a photocatalyst remains underexplored. Here we describe a photoinduced copper-catalyzed method for coupling readily available racemic tertiary alkyl chloride electrophiles with amines to generate fully substituted stereocenters with high enantioselectivity. The reaction proceeds at –40°C under excitation by a blue light-emitting diode and benefits from the use of a single, Earth-abundant transition metal acting as both the photocatalyst and the source of asymmetric induction. An enantioconvergent mechanism transforms the racemic starting material into a single product enantiomer

Production and preliminary characteristics of polyclonal antibodies specific to SSTR2A and SSTR5 receptors in pituitary

Wzrastające zainteresowanie receptorami somatostatyny (SSTR) wynika przede wszystkim z ich udziału w regulacji sekrecji hormonów oraz roli, jaką odgrywają w leczeniu analogami somatostatyny pacjentów z guzami przysadki. Skuteczność takiego leczenia uzależniona jest miedzy innymi od ekspresji na poziomie białkowym danego receptora w tkance, do określenia której konieczne są swoiste przeciwciała. W niniejszej pracy przedstawiliśmy założenia konieczne do otrzymywania oraz wstępną charakterystykę szeregu poliklonalnych przeciwciał skierowanych przeciwko części wewnątrzkomórkowej C-końca oraz zewnątrzkomórkowej N-końca receptorów SSTR-2A i SSTR-5. Przeciwciała te wykazywały wysoką swoistość w stosunku do peptydów użytych do immunizacji zwierząt, niskie wiązanie krzyżowe z innymi peptydami sekwencji aminokwasowej receptorów oraz reagowały z receptorami SSTR2A i SSTR5 w immunoblotingu i immunohistochemii.Pozytywna weryfikacja specyficzności otrzymanych przeciwciał pozwoliłaby na zwiększenie możliwości badawczych dotyczących struktury i posttranslacyjnych modyfikacji SSTR oraz częściowe uniezależnienie od rynku komercyjnego.The increasing interest in somatostatin receptors (SSTR) is mainly due to their involvement in the regulation of hormone secretion and the role in somatostatin analogue treatment of patients with pituitary adenomas. The efficiency of this treatment is highly dependent on receptor expression in tissue which on the protein level requires specific anti-receptor antibodies for testing.In this paper we introduced the principles for the production of several polyclonal antibodies specific for C-terminal intracellular part or N-terminal extracellular part of SSTR2A and SSTR5 receptors. The antibodies were highly specific for peptides used for immunization of animals, had low cross-reaction activities for other SSTR2A and SSTR5 peptides and reacted with receptors on immunoblots and in immunohistochemistry. The final verification of the antibodies’ specificity would allow us to perform the research concerning the structure and posttranslational modifications of SSTR and avoid dependency of commercial sources

Design, synthesis, and antimicrobial evaluation of a novel bone-targeting bisphosphonate-ciprofloxacin conjugate for the treatment of osteomyelitis biofilms

Osteomyelitis is a major problem worldwide and is devastating due to the potential for limb-threatening sequelae and mortality. Osteomyelitis pathogens are bone-attached biofilms, making antibiotic delivery challenging. Here we describe a novel osteoadsorptive bisphosphonate-ciprofloxacin conjugate (BV600022), utilizing a “target and release” chemical strategy, which demonstrated a significantly enhanced therapeutic index versus ciprofloxacin for the treatment of osteomyelitis in vivo. In vitro antimicrobial susceptibility testing of the conjugate against common osteomyelitis pathogens revealed an effective bactericidal profile and sustained release of the parent antibiotic over time. Efficacy and safety were demonstrated in an animal model of periprosthetic osteomyelitis, where a single dose of 10 mg/kg (15.6 μmol/kg) conjugate reduced the bacterial load by 99% and demonstrated nearly an order of magnitude greater activity than the parent antibiotic ciprofloxacin (30 mg/kg, 90.6 μmol/kg) given in multiple doses. Conjugates incorporating a bisphosphonate and an antibiotic for bone-targeted delivery to treat osteomyelitis biofilm pathogens constitute a promising approach to providing high bone-antimicrobial potency while minimizing systemic exposure

Procjena varijabli stanja sustava s gorivnim člankom i uzlaznim pretvaračem metodom brzog uzorkovanja signala

Estimation of state variables of a peak current mode (PCM) controlled DC-DC boost converter supplied by a PEM fuel cell is described in this paper. Since this system is highly nonlinear and non-minimum phase, its state variables are estimated by using fast output sampling method. Estimated state variables are the converter output voltage and its first derivative, and they are suitable for model reference adaptive control or sliding mode based control techniques. The estimator has been designed in a way that it gives a good estimate of the state variables in the continuous and in the discontinuous conduction mode of the converter, and in the presence of measurement and process noise caused by converter switching-mode operation. Experimental results of estimating the state variables on a 450 W boost converter supplied by the emulator of the PEM fuel cell BCS 64-32 show good results of the estimation, regardless of the conduction mode of the converter, i.e. the operating point determined by its output current.U ovom radu obrađena je procjena varijabli stanja sustava s istomjernim uzlaznim pretvaračem u vršnom strujnom načinu upravljanja napajanim PEM gorivnim člankom. Budući da je taj sustav izrazito nelinearan te neminimalno-fazan, za procjenu njegovih varijabli stanja upotrebljena je metoda brzog uzorkovanja izlaznog signala. Procjenjene varijable stanja su izlazni napon uzlaznog pretvarača te njegova prva derivacija, te su pogodne za adaptivno upravljanje s referentnim modelom i upravljanje temeljeno na kliznim režimima. Procjenitelj je projektiran na način da daje dobru procjenu varijabli stanja u kontinuiranom i diskontinuiranom režimu rada pretvarača, te u uvjetima mjernog i procesnog šuma uzrokovanog sklopnim načinom rada pretvarača. Eksperimentalni rezultati procjene varijabli stanja na uzlaznom pretvaraču snage 450 W napajanim emulatorom gorivnog članka BCS 64-32 pokazuju dobre rezultate procjene, neovisno o režimu rada pretvarača, odnosno radnoj točki određenoj njegovom izlaznom strujom

Comparison of Hepatic and Nephric Total Mercury Concentrations Between Feral and Ranch American Mink (Neovison vison) from Northwestern Poland

For many years the American mink (Neovison vison) has been used in North America (where it originates from) as a sensitive indirect bioindicator in assessing the degree of mercury (Hg) contamination in terrestrial ecosystems. The aim of this paper was the determination of total concentrations of Hg in the liver and kidneys of feral and ranch mink from the Warta Mouth National Park (WMNP) and from farms located in northwestern Poland, for comparison with similar data on American mink from North America. In road-killed feral mink from the WMNP, the mean concentrations were 11.8 and 14.1 mg/kg dry weight in the liver and kidney, respectively. Mean Hg concentrations in feral mink were from 240 to 90 times higher in these two respective tissues than in ranch mink. The feral mink from northwestern Poland had concentrations of hepatic and nephric Hg similar to the highest concentrations that have been recorded over the past several decades in wild American mink from certain areas of Canada and the USA

Chelating N-heterocyclic carbene-carboranes offer flexible ligand coordination to IrIII, RhIII and RuII: effect of ligand cyclometallation in catalytic transfer hydrogenation

Imidazolium salts linked by an ethyl tether to closo-dicarbadodecaboranes were reacted with [IrCp*Cl2]2, [RhCp*Cl2]2 or [Ru(p-cymene)Cl2]2 in the presence of Ag2O to prepare complexes of the type [MCp*(NHC)Cl2] (M = Ir, Rh; NHC = N-heterocyclic carbene) or [Ru(p-cymene)(NHC)Cl2]. When the NHC contained an N-tBu substituent, C–H activation of the tBu and subsequent alkyl coordination was observed at Ir. Coordination of the closo-dicarbadodecaborane moiety to Ir was possible to give 7-membered metallacycles, coordinated through the carbenic carbon of the NHC and either a carbon atom or a boron atom of the carborane. Examination of the Ir complexes in the transfer hydrogenation of acetophenone to 1-phenylethanol reveals that cyclometallation of the carborane moiety is important for catalytic efficacy, indicating a bifunctional mechanism and involvement of the dicarbadodecaborane anion