Low Expression of DYRK2 (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2) Correlates with Poor Prognosis in Colorectal Cancer.

Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) is a member of dual-specificity kinase family, which could phosphorylate both Ser/Thr and Tyr substrates. The role of DYRK2 in human cancer remains controversial. For example, overexpression of DYRK2 predicts a better survival in human non-small cell lung cancer. In contrast, amplification of DYRK2 gene occurs in esophageal/lung adenocarcinoma, implying the role of DYRK2 as a potential oncogene. However, its clinical role in colorectal cancer (CRC) has not been explored. In this study, we analyzed the expression of DYRK2 from Oncomine database and found that DYRK2 level is lower in primary or metastatic CRC compared to adjacent normal colon tissue or non-metastatic CRC, respectively, in 6 colorectal carcinoma data sets. The correlation between DYRK2 expression and clinical outcome in 181 CRC patients was also investigated by real-time PCR and IHC. DYRK2 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues. Functional studies confirmed that DYRK2 inhibited cell invasion and migration in both HCT116 and SW480 cells and functioned as a tumor suppressor in CRC cells. Furthermore, the lower DYRK2 levels were correlated with tumor sites (P = 0.023), advanced clinical stages (P = 0.006) and shorter survival in the advanced clinical stages. Univariate and multivariate analyses indicated that DYRK2 expression was an independent prognostic factor (P < 0.001). Taking all, we concluded that DYRK2 a novel prognostic biomarker of human colorectal cancer

Efficiency Enhancement in Polymer Solar Cells With a Polar Small Molecule Both at Interface and in the Bulk Heterojunction Layer

The polar molecules, including ferroelectric materials with large dipole moments, have been applied as interfacial layers to increase the efficiency of organic solar cells by increasing the bounded charge separation, tuning the energy levels, etc. Here, we report a small polar molecule 2-cyano-3- (4-(diphenylamino) phenyl)acrylic acid (TPACA) that can be either blended in the active layer or at the polymer/electrode interface to increase the efficiency of organic solar cell devices after poling. It is found that the built-in potential of the device is increased by 0.2 V after poling under negative bias. Blending TPACA into the active layer has shown to be a universal method to increase the efficiency of polymer solar cells. The efficiency is increased by 30–90% for all the polymer:fullerene systems tested, with the highest efficiency reaching 7.83% for the poly[4,8-bis-(2-ethyl-hexyl-thiophene-5-yl)-benzo[1,2-b:4,5-b’]dithiophene-2,6-diyl]-alt-[2-(2’-ethyl-hexanoyl)-thieno[3,4-b]thiophen-4,6-diyl]: [6,6]-phenyl-C71 -butyric acid methyl ester (PBDTTT-CT:PC70BM) system

Rigorous assessment and integration of the sequence and structure based features to predict hot spots

Background Systematic mutagenesis studies have shown that only a few interface residues termed hot spots contribute significantly to the binding free energy of protein-protein interactions. Therefore, hot spots prediction becomes increasingly important for well understanding the essence of proteins interactions and helping narrow down the search space for drug design. Currently many computational methods have been developed by proposing different features. However comparative assessment of these features and furthermore effective and accurate methods are still in pressing need. Results In this study, we first comprehensively collect the features to discriminate hot spots and non-hot spots and analyze their distributions. We find that hot spots have lower relASA and larger relative change in ASA, suggesting hot spots tend to be protected from bulk solvent. In addition, hot spots have more contacts including hydrogen bonds, salt bridges, and atomic contacts, which favor complexes formation. Interestingly, we find that conservation score and sequence entropy are not significantly different between hot spots and non-hot spots in Ab+ dataset (all complexes). While in Ab- dataset (antigen-antibody complexes are excluded), there are significant differences in two features between hot pots and non-hot spots. Secondly, we explore the predictive ability for each feature and the combinations of features by support vector machines (SVMs). The results indicate that sequence-based feature outperforms other combinations of features with reasonable accuracy, with a precision of 0.69, a recall of 0.68, an F1 score of 0.68, and an AUC of 0.68 on independent test set. Compared with other machine learning methods and two energy-based approaches, our approach achieves the best performance. Moreover, we demonstrate the applicability of our method to predict hot spots of two protein complexes. Conclusion Experimental results show that support vector machine classifiers are quite effective in predicting hot spots based on sequence features. Hot spots cannot be fully predicted through simple analysis based on physicochemical characteristics, but there is reason to believe that integration of features and machine learning methods can remarkably improve the predictive performance for hot spots

Rigorous assessment and integration of the sequence and structure based features to predict hot spots

<p>Abstract</p> <p>Background</p> <p>Systematic mutagenesis studies have shown that only a few interface residues termed hot spots contribute significantly to the binding free energy of protein-protein interactions. Therefore, hot spots prediction becomes increasingly important for well understanding the essence of proteins interactions and helping narrow down the search space for drug design. Currently many computational methods have been developed by proposing different features. However comparative assessment of these features and furthermore effective and accurate methods are still in pressing need.</p> <p>Results</p> <p>In this study, we first comprehensively collect the features to discriminate hot spots and non-hot spots and analyze their distributions. We find that hot spots have lower relASA and larger relative change in ASA, suggesting hot spots tend to be protected from bulk solvent. In addition, hot spots have more contacts including hydrogen bonds, salt bridges, and atomic contacts, which favor complexes formation. Interestingly, we find that conservation score and sequence entropy are not significantly different between hot spots and non-hot spots in Ab+ dataset (all complexes). While in Ab- dataset (antigen-antibody complexes are excluded), there are significant differences in two features between hot pots and non-hot spots. Secondly, we explore the predictive ability for each feature and the combinations of features by support vector machines (SVMs). The results indicate that sequence-based feature outperforms other combinations of features with reasonable accuracy, with a precision of 0.69, a recall of 0.68, an F1 score of 0.68, and an AUC of 0.68 on independent test set. Compared with other machine learning methods and two energy-based approaches, our approach achieves the best performance. Moreover, we demonstrate the applicability of our method to predict hot spots of two protein complexes.</p> <p>Conclusion</p> <p>Experimental results show that support vector machine classifiers are quite effective in predicting hot spots based on sequence features. Hot spots cannot be fully predicted through simple analysis based on physicochemical characteristics, but there is reason to believe that integration of features and machine learning methods can remarkably improve the predictive performance for hot spots.</p

Balanced Reward-inspired Reinforcement Learning for Autonomous Vehicle Racing

Autonomous vehicle racing has attracted extensive interest due to its great potential in autonomous driving at the extreme limits. Model-based and learning-based methods are being widely used in autonomous racing. However, model-based methods cannot cope with the dynamic environments when only local perception is available. As a comparison, learning-based methods can handle complex environments under local perception. Recently, deep reinforcement learning (DRL) has gained popularity in autonomous racing. DRL outperforms conventional learning- based methods by handling complex situations and leveraging local information. DRL algorithms, such as the proximal policy algorithm, can achieve a good balance between the execution time and safety in autonomous vehicle competition. However, the training outcomes of conventional DRL methods exhibit inconsistent correctness in decision-making. The instability in decision-making introduces safety concerns in autonomous vehicle racing, such as collisions into track boundaries. The proposed algorithm is capable to avoid collisions and improve the training quality. Simulation results on a physical engine demonstrate that the proposed algorithm outperforms other DRL algorithms in achieving safer control during sharp bends, fewer collisions into track boundaries, and higher training quality among multiple tracks

GFI1 downregulation promotes inflammation-linked metastasis of colorectal cancer.

Inflammation is frequently associated with initiation, progression, and metastasis of colorectal cancer (CRC). Here, we unveil a CRC-specific metastatic programme that is triggered via the transcriptional repressor, GFI1. Using data from a large cohort of clinical samples including inflammatory bowel disease and CRC, and a cellular model of CRC progression mediated by cross-talk between the cancer cell and the inflammatory microenvironment, we identified GFI1 as a gating regulator responsible for a constitutively activated signalling circuit that renders CRC cells competent for metastatic spread. Further analysis of mouse models with metastatic CRC and human clinical specimens reinforced the influence of GFI1 downregulation in promoting CRC metastatic spread. The novel role of GFI1 is uncovered for the first time in a human solid tumour such as CRC. Our results imply that GFI1 is a potential therapeutic target for interfering with inflammation-induced CRC progression and spread

Comparison of pretrained transformer-based models for influenza and COVID-19 detection using social media text data in Saskatchewan, Canada

BackgroundThe use of social media data provides an opportunity to complement traditional influenza and COVID-19 surveillance methods for the detection and control of outbreaks and informing public health interventions.ObjectiveThe first aim of this study is to investigate the degree to which Twitter users disclose health experiences related to influenza and COVID-19 that could be indicative of recent plausible influenza cases or symptomatic COVID-19 infections. Second, we seek to use the Twitter datasets to train and evaluate the classification performance of Bidirectional Encoder Representations from Transformers (BERT) and variant language models in the context of influenza and COVID-19 infection detection.MethodsWe constructed two Twitter datasets using a keyword-based filtering approach on English-language tweets collected from December 2016 to December 2022 in Saskatchewan, Canada. The influenza-related dataset comprised tweets filtered with influenza-related keywords from December 13, 2016, to March 17, 2018, while the COVID-19 dataset comprised tweets filtered with COVID-19 symptom-related keywords from January 1, 2020, to June 22, 2021. The Twitter datasets were cleaned, and each tweet was annotated by at least two annotators as to whether it suggested recent plausible influenza cases or symptomatic COVID-19 cases. We then assessed the classification performance of pre-trained transformer-based language models, including BERT-base, BERT-large, RoBERTa-base, RoBERT-large, BERTweet-base, BERTweet-covid-base, BERTweet-large, and COVID-Twitter-BERT (CT-BERT) models, on each dataset. To address the notable class imbalance, we experimented with both oversampling and undersampling methods.ResultsThe influenza dataset had 1129 out of 6444 (17.5%) tweets annotated as suggesting recent plausible influenza cases. The COVID-19 dataset had 924 out of 11939 (7.7%) tweets annotated as inferring recent plausible COVID-19 cases. When compared against other language models on the COVID-19 dataset, CT-BERT performed the best, supporting the highest scores for recall (94.8%), F1(94.4%), and accuracy (94.6%). For the influenza dataset, BERTweet models exhibited better performance. Our results also showed that applying data balancing techniques such as oversampling or undersampling method did not lead to improved model performance.ConclusionsUtilizing domain-specific language models for monitoring users’ health experiences related to influenza and COVID-19 on social media shows improved classification performance and has the potential to supplement real-time disease surveillance

The existence of Th22, pure Th17 and Th1 cells in CIN and Cervical Cancer along with their frequency variation in different stages of cervical cancer

BACKGROUND: Recently, it is found that T-helper (Th) 22 cells are involved in different types of autoimmune and tumor diseases. But, till now, no study has been carried out to understand the involvement of these cells in cervical cancer (CC). METHODS: Flow cytometry was used to determine the expression of interferon gamma (IFN-gamma), Interleukin-22 (IL-22), IL-17 in the peripheral blood of healthy controls (HC), CIN and cervical cancer patients. From peripheral blood mononuclear cells (PBMCs), mRNA expression levels of Aryl hydrocarbon receptor (AHR), RAR-related orphan receptor C (RORC), TNF-alpha and IL-6 were respectively determined. Using the method of ELISA, plasma concentrations of IL-22, IL-17 and TNF-alpha were examined. RESULTS: Th22 and Th17 cells were elevated in CC and CIN patients. Th1 cells and the plasma concentrations of IL-22 in CC patients were significantly increased compared with HC. In CC patients, an increased prevalence of Th22 cells was associated with lymph node metastases. There was a positive correlation between Th22 and Th17 cells, but an approximately negative correlation between Th22 and Th1 cells in CC patients. The mRNA expression of RORC, TNF-alpha and IL-6 was significantly high in CC patients. CONCLUSIONS: Our results indicate that there is a higher circulatory frequency of Th22, Th17 and Th1 cells in CC which may conjointly participate in the pathogenesis and growth of CC.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Polyelectrolyte interlayers with a broad processing window for high efficiency inverted organic solar cells towards mass production

Neutral polyelectrolyte interfacial layers in organic solar cells are well-known for their ability to tailor the work function of electrodes, improve charge carrier extraction and maximize open circuit voltage. However, they also suffer from low charge carrier conductivity, and therefore the interlayer must be kept thin, which in turn requires very precise deposition. This prerequisite significantly reduces the robustness of the fabrication process and makes such structures difficult to up-scale for roll-to-roll mass production. Herein, we find that by washing the polyelectrolyte layer with N,N-dimethylformamide (DMF) after deposition, solar cell efficiency jumps to near optimum levels, no matter what the original thickness of the polyelectrolyte layer. Subsequent characterization of the DMF-washed ZnO/PEI interlayer reveals a changed surface structure, passivated surface trap states, and thus improved transport properties and lower recombination losses. We demonstrate the general applicability of the method to other state-of-the-art material systems, namely P3HT:ICBA, PTB7:PC71BM and PTB7-Th:PC71BM. We find that the more efficient the material system, the larger the improvement in efficiency after DMF washing. Thus, this method represents a general way to relax the fabrication criteria for high efficiency organic solar cells. We anticipate that this method could be of use in other classes of devices such as OTFTs and OLEDs