Quinnwelch2054

Event extraction is essential for natural language processing. In the biomedical field, the nested event phenomenon (event A as a participating role of event B) makes extracting this event more difficult than extracting a single event. Therefore, the performance of nested biomedical events is always underwhelming. In addition, previous works relied on a pipeline to build an event extraction model, which ignored the dependence between trigger recognition and event argument detection tasks and produced significant cascading errors.

This study aims to design a unified framework to jointly train biomedical event triggers and arguments and improve the performance of extracting nested biomedical events.

We proposed an end-to-end joint extraction model that considers the probability distribution of triggers to alleviate cascading errors. Moreover, we integrated the syntactic structure into an attention-based gate graph convolutional network to capture potential interrelations between triggers and related entities, which improved the performance of extracting nested biomedical events.

The experimental results demonstrated that our proposed method achieved the best F1 score on the multilevel event extraction biomedical event extraction corpus and achieved a favorable performance on the biomedical natural language processing shared task 2011 Genia event corpus.

Our conditional probability joint extraction model is good at extracting nested biomedical events because of the joint extraction mechanism and the syntax graph structure. Moreover, as our model did not rely on external knowledge and specific feature engineering, it had a particular generalization performance.

Our conditional probability joint extraction model is good at extracting nested biomedical events because of the joint extraction mechanism and the syntax graph structure. Moreover, as our model did not rely on external knowledge and specific feature engineering, it had a particular generalization performance.6-Aminocaproic acid (6ACA) is a key building block and an attractive precursor of caprolactam, which is used to synthesize nylon 6, one of the most common polymers manufactured nowadays. (Bio)-production of platform chemicals from renewable feedstocks is instrumental to tackle climate change and decrease fossil fuel dependence. Here, the cell-free biosynthesis of 6ACA from 6-hydroxycaproic acid was achieved using a co-immobilized multienzyme system based on horse liver alcohol dehydrogenase, Halomonas elongata transaminase, and Lactobacillus pentosus NADH oxidase for in-situ cofactor recycling, with >90 % molar conversion (m.c.) The integration of a step to synthesize hydroxy-acid from lactone by immobilized Candida antarctica lipase B resulted in >80 % m.c. of ϵ-caprolactone to 6ACA, >20 % of δ-valerolactone to 5-aminovaleric acid, and 30 % of γ-butyrolactone to γ-aminobutyric acid in one-pot batch reactions. Two serial packed-bed reactors were set up using these biocatalysts and applied to the continuous-flow synthesis of 6ACA from ϵ-caprolactone, achieving a space-time yield of up to 3.31 g6ACA  h-1  L-1 with a segmented liquid/air flow for constant oxygen supply.Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at six months, in particular cardio-vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.CRISPR/dCas9-based activation systems (CRISPRa) enable sequence-specific gene activation and are therefore of particular interest for the 'shock and kill' cure approach against HIV-1 infections. This approach aims to activate the latent HIV-1 proviruses in infected cells and subsequently kill these cells. Several CRISPRa systems have been shown to specifically and effectively activate latent HIV-1 when targeted to the HIV-1 5'LTR promoter, making them a promising 'shock' strategy. SC75741 Here, we aimed to evaluate the dCas9-VPR system for its applicability in reversing HIV-1 latency and identify the optimal gRNA target site in the HIV-1 5'LTR promoter leading to the strongest activation of the provirus with this system. We systematically screened the HIV-1 promoter by selecting 14 specific gRNAs that cover almost half of the HIV-1 promoter from the 3' half of the U3 until the beginning of the R region. Screening in several latently HIV-1 infected cell lines showed that dCas9-VPR leads to a high activation of HIV-1 and that gRNA-V and -VII induce the strongest activation of replication competent latent provirus. This data indicates that the optimal activation region in the HIV-1 promoter for the dCas9-VPR system is located -165 to -106 bp from the transcription start site and that it is consistent with the optimal activation region reported for other CRISPRa systems. Our data demonstrates that the dCas9-VPR system is a powerful tool for HIV-1 activation and could be harnessed for the 'shock and kill' cure approach.

The study of hypertrophic cardiomyopathy (HCM) can yield insight into the mechanisms underlying the complex trait of cardiac hypertrophy. To date, most genetic variants associated with HCM have been found in sarcomeric genes. Here, we describe a novel HCM-associated variant in the noncanonical Wnt signaling interactor

(Wilms tumor interacting protein) and provide evidence of a role for WTIP in complex disease.

In a family affected by HCM, we used exome sequencing and identity-by-descent analysis to identify a novel variant in WTIP (p.Y233F). We knocked down WTIP in isolated neonatal rat ventricular myocytes with lentivirally delivered short hairpin ribonucleic acids and in

via morpholino injection. We performed weighted gene coexpression network analysis for WTIP in human cardiac tissue, as well as association analysis for WTIP variation and left ventricular hypertrophy. Finally, we generated induced pluripotent stem cell-derived cardiomyocytes from patient tissue, characterized size and calcium cychanism with implications across diverse forms of cardiac hypertrophy.

We demonstrate that a novel genetic variant found in a family with HCM disrupts binding to a known Wnt signaling protein, misregulating cardiomyocyte calcium dynamics. Further, in orthogonal model systems, we show that expression of the gene WTIP is important in complex cardiac hypertrophy phenotypes. These findings, derived from the observation of a rare Mendelian disease variant, uncover a novel disease mechanism with implications across diverse forms of cardiac hypertrophy.Coptis chinensis inflorescence is a by-product of Coptis chinensis Franch and riches in alkaloids. We screened the bioactive compounds in the by-product through an immobilized peroxisome proliferator-activated receptor gamma. The receptor was covalently immobilized on the macroporous silica gel through amino groups to generate the affinity stationary phase and was applied for screening. Berberine, palmatine, and jatrorrhizine were identified as the retained components of the herb on the affinity column. We evaluated the binding of the three bioactive compounds with the receptor by nonlinear chromatography and molecular docking. The affinities of the compounds to the receptor were (1.42 ± 0.10) ×108 /M, (4.88 ± 0.38) ×107 /M, and (1.65 ± 0.13) ×107 /M for berberine, palmatine, and jatrorrhizine, with dissociation rate constants of (17.70 ± 0.03) ×10-3 /S, (5.18 ± 0.25) ×10-2 /S, and (15.7 ± 0.05) ×10-2 /S, respectively. Cys285, Arg288, Ile326, Leu330, and His449 in the agonist binding pocket of the receptor participated in the formation of bioactive compound-receptor conjugates. These data indicated that the immobilized receptor is a reliable alternative for screening the bioactive compounds. In addition, Coptis chinensis inflorescence has the potential to be a source for drug discovery.Understanding the genomic and epigenetic mechanisms of drug resistance in pediatric acute lymphoblastic leukemia (ALL) is critical for further improvements in treatment outcomes. The role of transcriptomic response in conferring resistance to l-asparaginase (LASP) is poorly understood beyond asparagine synthetase (ASNS). We defined reproducible LASP response genes in LASP-resistant and LASP-sensitive ALL cell lines as well as primary leukemia samples from newly diagnosed patients. Defining target genes of the amino acid stress response-related transcription factor activating transcription factor 4 (ATF4) in ALL cell lines using chromatin immunoprecipitation sequencing (ChIP-seq) revealed 45% of genes that changed expression after LASP treatment were direct targets of the ATF4 transcription factor, and 34% of these genes harbored LASP-responsive ATF4 promoter binding events. SLC7A11 was found to be a response gene in cell lines and patient samples as well as a direct target of ATF4. SLC7A11 was also one of only 2.4% of LASP response genes with basal level gene expression that also correlated with LASP ex vivo resistance in primary leukemia cells. Experiments using chemical inhibition of SLC7A11 with sulfasalazine, gene overexpression, and partial gene knockout recapitulated LASP resistance or sensitivity in ALL cell lines. These findings show the importance of assessing changes in gene expression following treatment with an antileukemic agent for its association with drug resistance and highlight that many response genes may not differ in their basal expression in drug-resistant leukemia cells.Carbon dots (CDs) are 10-nm nanomaterial classes as excellent candidates in various applications physics, biology, chemistry, and food science due to high stable biocompatibility and high surface expansive. CDs produced from natural materials have received wide attention due to their unique benefits, easy availabilities, sufficient costs, and harmless to the ecosystem. The various properties of CDs can be obtained from various synthesis methods hydrothermal, microwave-assisted, and pyrolysis. The CDs have shown enormous potential in metal particle detection, colorimetric sensors, electrochemical sensors, and pesticide sensors. This review provides systematic information on a synthesis method based on natural resources and the application to the environmental sensors for supporting the clean environment. We hope this review will be useful as a reference source in providing the guidance or roadmap for new researchers to develop new strategies in increasing luminescence properties CDs for multi detection of heavy metals in the environment.