Miracle-dz/UniFAR-FTUs huggingface dataset:
Resistance to QoI (Strobilurin-like) Fungicides in Isolates of Pyricularia grisea from Perennial Ryegrass.

In August 2000, azoxystrobin was ineffective in controlling gray leaf spot of perennial ryegrass at a golf course in Lexington, KY and at two golf courses in Illinois. Isolates suspected of being fungicide-resistant ("suspect isolates") were compared to "baseline" isolates obtained from sites with no known use of quinol-oxidizing inhibitor (QoI) fungicides. Conidial germination of Pyricularia grisea was tested in vitro with 100 μg of salicylhydroxamic acid per ml. For baseline isolates, 50% effective concentration (EC50) values for azoxystrobin and trifloxystrobin were 0.015 to 0.064 and 0.013 to 0.078 μg/ml, respectively; EC50 values for suspect isolates were 2.39 to 44.8 and 0.31 to 111, respectively. All suspect isolates exhibited significantly (P = 0.05) lower sensitivity to QoI fungicides than all baseline isolates. The mean EC50 values for suspect isolates for azoxystrobin and trifloxystrobin were 690 and 827 times higher, respectively, than the means for baseline isolates. In the laboratory, azoxystrobin and trifloxystrobin provided essentially complete control of disease induced by nine baseline isolates in vivo. Azoxystrobin and trifloxystrobin provided poor to no control of disease induced by six of eight suspect isolates; control of disease induced by the remaining two isolates was partial for azoxystrobin and complete for trifloxystrobin. We conclude that one or more biotypes of perennial ryegrass-infecting strains of P. grisea with resistance to QoI fungicides have emerged. This is the first report of resistance to QoI fungicides in P. grisea. Furthermore, this is one of two QoIresistant fungal pathogens collected in the United States during the 2000 growing season, the first instances reported for North America.
The deSUMOylase SENP2 coordinates homologous recombination and nonhomologous end joining by independent mechanisms

SUMOylation in the DNA double-strand break (DSB) response regulates recruitment, activity and clearance of repair factors. However, our understanding of a role for deSUMOylation in this process is limited. Here we identify different mechanistic roles for deSUMOylation in homologous recombination (HR) and non-homologous enjoining (NHEJ) through the investigation of the deSUMOylase SENP2. We find regulated deSUMOylation of MDC1 prevents excessive SUMOylation and its RNF4-VCP mediated clearance from DSBs, thereby promoting NHEJ. In contrast we show HR is differentially sensitive to SUMO availability and SENP2 activity is needed to provide SUMO. SENP2 is amplified as part of the chromosome 3q amplification in many cancers. Increased SENP2 expression prolongs MDC1 foci retention and increases NHEJ and radioresistance. Collectively our data reveal that deSUMOylation differentially primes cells for responding to DSBs and demonstrates the ability of SENP2 to tune DSB repair responses.
Complete mitogenomic sequence of the Critically Endangered Northern River Shark Glyphis garricki (Carcharhiniformes: Carcharhinidae)

Abstract In this study we describe the first complete mitochondrial sequence for the Critically Endangered Northern River shark Glyphis garricki. The complete mitochondrial sequence is 16,702 bp in length, contains 37 genes and one control region with the typical gene order and transcriptional direction of vertebrate mitogenomes. The overall base composition is 31.5% A, 26.3% C, 12.9% G and 29.3% T. The length of 22 tRNA genes ranged from 68 (tRNA-Ser2 and tRNA-Cys) to 75 (tRNA-Leu1) bp. The control region of G. garricki was 1067 bp in length with high A + T (67.9%) and poor G (12.6%) content. The mitogenomic characters (base composition, codon usage and gene length) of G. garricki were very similar to Glyphis glyphis.
Bearing Fault Diagnosis Method Based on Deep Convolutional Neural Network and Random Forest Ensemble Learning

Recently, research on data-driven bearing fault diagnosis methods has attracted increasing attention due to the availability of massive condition monitoring data. However, most existing methods still have difficulties in learning representative features from the raw data. In addition, they assume that the feature distribution of training data in source domain is the same as that of testing data in target domain, which is invalid in many real-world bearing fault diagnosis problems. Since deep learning has the automatic feature extraction ability and ensemble learning can improve the accuracy and generalization performance of classifiers, this paper proposes a novel bearing fault diagnosis method based on deep convolutional neural network (CNN) and random forest (RF) ensemble learning. Firstly, time domain vibration signals are converted into two dimensional (2D) gray-scale images containing abundant fault information by continuous wavelet transform (CWT). Secondly, a CNN model based on LeNet-5 is built to automatically extract multi-level features that are sensitive to the detection of faults from the images. Finally, the multi-level features containing both local and global information are utilized to diagnose bearing faults by the ensemble of multiple RF classifiers. In particular, low-level features containing local characteristics and accurate details in the hidden layers are combined to improve the diagnostic performance. The effectiveness of the proposed method is validated by two sets of bearing data collected from reliance electric motor and rolling mill, respectively. The experimental results indicate that the proposed method achieves high accuracy in bearing fault diagnosis under complex operational conditions and is superior to traditional methods and standard deep learning methods.
An Exploration of Useful Telemedicine-Based Resources for Clinical Research.

BACKGROUND Clinical trials are key to ensuring high-quality, effective, and safe health care interventions, but there are many barriers to their successful and timely implementation. Difficulties with participant recruitment and enrollment are largely affected by difficulties with obtaining informed consent. Teleconsent is a telemedicine- based approach to obtaining informed consent and offers a unique solution to limitations of traditional consent approaches. METHODS We conducted a survey among 134 clinical trial researchers in academic/university-, industry-, and clinically based settings. The survey addressed important aspects of teleconsent, potential teleconsent enhancements, and other telehealth capabilities to support clinical research. RESULTS The majority of respondents viewed teleconsent as an important approach for obtaining informed consent and indicated that they would likely use teleconsent if available. Consenting participants at remote sites, increasing access to clinical trials, and consenting participants in their homes were viewed as the greatest opportunities for teleconsent. Features for building, validating, and assessing understanding of teleconsent forms, mobile capabilities, three-way teleconsent calls, and direct links to forms via recruitment websites were viewed as important teleconsent enhancements. Other telehealth capabilities to support clinical research, including surveys, file transfer, three-way video, screenshare, and photo capture during telemedicine visits, and proposed telemedicine capabilities such as video call recording, ID information capture, and integration of medical devices, were also viewed as important. CONCLUSIONS Teleconsent and telemedicine are promising solutions to some common challenges to clinical trials. Many barriers to study recruitment and enrollment might be overcome by investing time and resources and further evaluating this technology.
Provable Data Integrity in the Pharmaceutical Industry Based on Version Control Systems and the Blockchain

In the pharmaceutical industry, process validation tasks are based on the raw data and its derived analytical results generated from the process. Process validation failure affects both patient safety and the economic success of the manufacturing company. Hence, data integrity is highly critical in this area. Regulatory agencies, such as the Food and Drug Administration (FDA), reacted to past data integrity breaches by publishing new guidelines on data integrity for the correct handling of data in the pharmaceutical context. In this contribution, we want to show how data integrity can be improved on a technological level, removing the need for trusted third parties and centralized systems for this task. Therefore, we implemented an approach that uses existing tools, currently mostly used by software developers, and combined them with a new smart contract built on top of the Ethereum blockchain. In a case study, we test how data manipulation or backdating of results can be easily detected and how regulatory agencies can audit the complete data flow from the regulatory report back to the original raw data. The results of this contribution outline a possible road map for the development of production-ready tools, such as versioned database systems that natively interoperate with distributed ledgers. This will improve the trustworthiness of pharmaceutical manufacturing data by both protecting the intellectual property of the industrial company and improving the safety of the patients. LAY ABSTRACT: In the pharmaceutical industry, economically driven manufacturing companies are regulated and controlled by regulatory agencies. The pharmaceutical manufacturing companies need to produce large amounts of process and analytical data to show that their products are safe for patients. As the decisions of the regulatory agencies rely on this data, manufacturing companies need to prove how their generated data can be protected from technical breaches or data manipulation. As of today, the available technical solutions to provide data integrity are not working well enough. Regulatory agencies have published multiple documents highlighting the current data integrity issues. In this contribution, we show how blockchain, a technology that multiple cryptocurrencies like Bitcoin rely on, can help to improve the integrity of manufacturing data and data science analysis procedures. Therefore, we combined a smart contract on the Ethereum blockchain with tools currently mostly used by software developers. The presented workflow shows how data integrity can be guaranteed on a technological level without the need for trusted third parties.
Chemical cross‐linking of xenopericardial biomeshes: A bottom‐up study of structural and functional correlations

Decellularized bovine pericardium (DBP)‐based biomeshes are the gold standard in reconstructive surgery. In order to prolong their stability after the transplantation, various chemical cross‐linking strategies are employed. However, structural and functional properties of the biomeshes differ in dependence on the cross‐linker used. Here, we performed a bottom‐up study of structural and functional alterations of DBP‐based biomeshes following cross‐linking with hexamethylene diisocyanate (HMDC), ethylene glycol diglycidyl ether (EGDE), 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide (EDC) and genipin. The in vitro cytotoxicity tests supported their clinical applicability. Their structural differences (eg roughness, fibre thickness, pore morphology) were evaluated using the two‐photon confocal laser scanning, atomic force, scanning electron and polarized light microscopies. HMDC and EDC samples appeared to be the roughest. Complex mechanical trials indicated the tendency to reduced Young’s Modulus and mechanical anisotropy values of DBP upon cross‐linking. The lowest mechanical anisotropy was found in EDC and genipin sample groups. In vitro collagenase susceptibility was the highest for EDC samples and the lowest for EGDE samples. The comparative analysis of the results allowed us to recognize the strengths and weaknesses of each cross‐linker in relation to a particular clinical application.
Genetic Variation in Pan Species Is Shaped by Demographic History and Harbors Lineage-Specific Functions

Abstract Chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the closest living relatives of humans, but the two species show distinct behavioral and physiological differences, particularly regarding female reproduction. Despite their recent rapid decline, the demographic histories of the two species have been different during the past 1–2 Myr, likely having an impact on their genomic diversity. Here, we analyze the inferred functional consequences of genetic variation across 69 individuals, making use of the most complete data set of genomes in the Pan clade to date. We test to which extent the demographic history influences the efficacy of purifying selection in these species. We find that small historical effective population sizes (Ne) correlate not only with low levels of genetic diversity but also with a larger number of deleterious alleles in homozygosity and an increased proportion of deleterious changes at low frequencies. To investigate the putative genetic basis for phenotypic differences between chimpanzees and bonobos, we exploit the catalog of putatively deleterious protein-coding changes in each lineage. We show that bonobo-specific nonsynonymous changes are enriched in genes related to age at menarche in humans, suggesting that the prominent physiological differences in the female reproductive system between chimpanzees and bonobos might be explained, in part, by putatively adaptive changes on the bonobo lineage.
P-selectin drives complement attack on endothelium during intravascular hemolysis in TLR-4/heme-dependent manner

Significance Complement system activation occurs in sickle cell disease and other hemolytic disorders, but the pathological relevance and the acquisition of a complement-activating phenotype by host cells during hemolysis remain unclear. Here we demonstrated that intravascular hemolysis triggered liver damage, which was attenuated in C3-deficient mice or by C5 blockade, showing the importance of complement system for hemolysis-mediated tissue stress response. Heme-dependent complement deposits were detected on endothelium, appeared upon activation of TLR4, and were mediated by P-selectin. This resulted in unconventional complement activation, mediated by anchoring of C3(H2O) on endothelial surface. In conclusion, our data suggest that complement system could be a therapeutic target in hemolytic diseases, such as sickle cell disease. Hemolytic diseases are frequently linked to multiorgan failure subsequent to vascular damage. Deciphering the mechanisms leading to organ injury upon hemolytic event could bring out therapeutic approaches. Complement system activation occurs in hemolytic disorders, such as sickle cell disease, but the pathological relevance and the acquisition of a complement-activating phenotype during hemolysis remain unclear. Here we found that intravascular hemolysis, induced by injection of phenylhydrazine, resulted in increased alanine aminotransferase plasma levels and NGAL expression. This liver damage was at least in part complement-dependent, since it was attenuated in complement C3−/− mice and by injection of C5-blocking antibody. We evidenced C3 activation fragments’ deposits on liver endothelium in mice with intravascular hemolysis or injected with heme as well as on cultured human endothelial cells (EC) exposed to heme. This process was mediated by TLR4 signaling, as revealed by pharmacological blockade and TLR4 deficiency in mice. Mechanistically, TLR4-dependent surface expression of P-selectin triggered an unconventional mechanism of complement activation by noncovalent anchoring of C3 activation fragments, including the typical fluid-phase C3(H2O), measured by surface plasmon resonance and flow cytometry. P-selectin blockade by an antibody prevented complement deposits and attenuated the liver stress response, measured by NGAL expression, in the hemolytic mice. In conclusion, these results revealed the critical impact of the triad TLR4/P-selectin/complement in the liver damage and its relevance for hemolytic diseases. We anticipate that blockade of TLR4, P-selectin, or the complement system could prevent liver injury in hemolytic diseases like sickle cell disease.
Cardiovascular Effects of PCB 126 (3,3’,4,4’,5-Pentachlorobiphenyl) in Zebrafish Embryos and Impact of Co-Exposure to Redox Modulating Chemicals

The developing cardiovascular system of zebrafish is a sensitive target for many environmental pollutants, including dioxin-like compounds and pesticides. Some polychlorinated biphenyls (PCBs) can compromise the cardiovascular endothelial function by activating oxidative stress-sensitive signaling pathways. Therefore, we exposed zebrafish embryos to PCB126 or to several redox-modulating chemicals to study their ability to modulate the dysmorphogenesis produced by PCB126. PCB126 produced a concentration-dependent induction of pericardial edema and circulatory failure, and a concentration-dependent reduction of cardiac output and body length at 80 hours post fertilization (hpf). Among several modulators tested, the effects of PCB126 could be both positively and negatively modulated by different compounds; co-treatment with α-tocopherol (vitamin E liposoluble) prevented the adverse effects of PCB126 in pericardial edema, whereas co-treatment with sodium nitroprusside (a vasodilator compound) significantly worsened PCB126 effects. Gene expression analysis showed an up-regulation of cyp1a, hsp70, and gstp1, indicative of PCB126 interaction with the aryl hydrocarbon receptor (AhR), while the transcription of antioxidant genes (sod1, sod2; cat and gpx1a) was not affected. Further studies are necessary to understand the role of oxidative stress in the developmental toxicity of low concentrations of PCB126 (25 nM). Our results give insights into the use of zebrafish embryos for exploring mechanisms underlying the oxidative potential of environmental pollutants.
Using the past to contextualize anthropogenic impacts on the present and future distribution of an endemic Caribbean mammal

Island species are difficult to conserve because they face the synergy of climate change, invasive species, deforestation, and increasing human population densities in areas where land mass is shrinking. The Caribbean island of Hispaniola presents particular challenges because of geopolitical complexities that span 2 countries and hinder coordinated management of species across the island. We employed species distribution modeling to evaluate the impacts of climatic change and anthropogenic activities on the distribution of an endemic mammal of conservation concern, the Hispaniolan solenodon (Solenodon paradoxus). We aggregated occurrence points for this poorly known species for the Last Glacial Maximum (LGM) and the present (1975–2016) based on museum collections, online biodiversity databases, and new field surveys. We quantified degree of overlap between periods and scenarios with Schoener's D. Through a conservation paleobiology lens, we found that over time humans played an increasing role in shaping the distribution of S. paradoxus, thus, providing a foundation for developing conservation strategies on appropriate spatiotemporal scales. Human population density was the single most important predictor of S. paradoxus occurrence. Densities >166 people/km2 corresponded to a near‐zero probability of occurrence. Models that accounted for climate but not anthropogenic variables falsely identified suitable habitat in Haiti, where on‐the‐ground surveys confirm habitat is unavailable. Climate‐only models also significantly overestimated the potential for habitat connectivity between isolated populations. Our work highlights that alternative fates for S. paradoxus in the Anthropocene exist across the political border between the Dominican Republic and Haiti due to the fundamentally different economic and political realities of each country. Relationships in the fossil record confirm that Hispaniola's sociopolitical boundary is not biologically significant but instead represents one imposed on the island's fauna in the past 500 years by colonial activity. Our approach reveals how a paleontological perspective can contribute to concrete management insights.
Stereoselective Synthesis of Spiro-2-oxabicyclo[2.2.2]octane Enabled by Ag(I)/ Brønsted Acid Relay Catalysis.

A highly stereoselective synthesis of a spiro-cineole scaffold that contains four stereogenic centers from readily accessible 2-alkynylbenzaldehydes and styrenes under very mild reaction conditions was reported. This cascade reaction involves a Ag(I)-catalyzed alkyne cycloisomerization and oxa-[4 + 2]-cycloaddition to give an oxonium intermediate which subsequently undergoes a previously unexplored 1,2-alkyl migration to access highly strained spiro-2-oxabicyclo[2.2. 2]octanes in high yields with excellent stereoselectivities.
Automated Multiscale Approach To Predict Self-Diffusion from a Potential Energy Field

For large-scale screening studies there is a need to estimate the diffusion of gas molecules in nanoporous materials more efficiently than (brute force) molecular dynamics. In particular for systems with low diffusion coefficients molecular dynamics can be prohibitively expensive. An alternative is to compute the hopping rates between adsorption sites using transition state theory. For large-scale screening this requires the automatic detection of the transition states between the adsorption sites along the different diffusion paths. Here an algorithm is presented that analyzes energy grids for the moving particles. It detects the energies at which diffusion paths are formed, together with their directions. This allows for easy identification of nondiffusive systems. For diffusive systems, it partitions the grid coordinates assigned to energy basins and transitions states, permitting a transition state theory based analysis of the diffusion. We test our method on CH4 diffusion in zeolites, using a standard kinetic Monte Carlo simulation based on the output of our grid analysis. We find that it is accurate, fast, and rigorous without limitations to the geometries of the diffusion tunnels or transition states.