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Fan Xu ◽  
Yangjie Dan ◽  
Keyu Yan ◽  
Yong Ma ◽  
Mingwen Wang

Chinese dialects discrimination is a challenging natural language processing task due to scarce annotation resource. In this article, we develop a novel Chinese dialects discrimination framework with transfer learning and data augmentation (CDDTLDA) in order to overcome the shortage of resources. To be more specific, we first use a relatively larger Chinese dialects corpus to train a source-side automatic speech recognition (ASR) model. Then, we adopt a simple but effective data augmentation method (i.e., speed, pitch, and noise disturbance) to augment the target-side low-resource Chinese dialects, and fine-tune another target ASR model based on the previous source-side ASR model. Meanwhile, the potential common semantic features between source-side and target-side ASR models can be captured by using self-attention mechanism. Finally, we extract the hidden semantic representation in the target ASR model to conduct Chinese dialects discrimination. Our extensive experimental results demonstrate that our model significantly outperforms state-of-the-art methods on two benchmark Chinese dialects corpora.

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 183
Colin E. Evans

Inflammatory lung injury is characterized by lung endothelial cell (LEC) death, alveolar epithelial cell (AEC) death, LEC–LEC junction weakening, and leukocyte infiltration, which together disrupt nutrient and oxygen transport. Subsequently, lung vascular repair is characterized by LEC and AEC regeneration and LEC–LEC junction re-annealing, which restores nutrient and oxygen delivery to the injured tissue. Pulmonary hypoxia is a characteristic feature of several inflammatory lung conditions, including acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19). The vascular response to hypoxia is controlled primarily by the hypoxia-inducible transcription factors (HIFs) 1 and 2. These transcription factors control the expression of a wide variety of target genes, which in turn mediate key pathophysiological processes including cell survival, differentiation, migration, and proliferation. HIF signaling in pulmonary cell types such as LECs and AECs, as well as infiltrating leukocytes, tightly regulates inflammatory lung injury and repair, in a manner that is dependent upon HIF isoform, cell type, and injury stimulus. The aim of this review is to describe the HIF-dependent regulation of inflammatory lung injury and vascular repair. The review will also discuss potential areas for future study and highlight putative targets for inflammatory lung conditions such as ALI/ARDS and severe COVID-19. In the development of HIF-targeted therapies to reduce inflammatory lung injury and/or enhance pulmonary vascular repair, it will be vital to consider HIF isoform- and cell-specificity, off-target side-effects, and the timing and delivery strategy of the therapeutic intervention.

2022 ◽  
pp. 1-6
Anadil Javaid ◽  
Jared Mathai ◽  
David Song ◽  
Stephen Brown

Sunitinib is a tyrosine kinase inhibitor that is frequently used in the treatment of metastatic renal cell carcinoma (mRCC). As a multikinase inhibitor, numerous off-target side effects of this medication are widely recognized. More recently, endocrine side effects, including hypoadrenalism, are becoming more apparent. We report a case in which a 71-year-old female experienced recurrent adrenal crises when managed with sunitinib for mRCC on a background of immune-related hypopituitarism and hypoadrenalism as a result of previous treatment with immunotherapy. Clinicians should be aware of this potential toxicity when using such medications and consider further investigation in the appropriate clinical setting.

2021 ◽  
Vol 3 (12) ◽  
Nathan D. McDonald ◽  
Courtney E. Love ◽  
Henry S. Gibbons

The global use of organophosphate insecticides (OPPs) and the growing concern of off-target side effects due to OPP exposure has prompted the need for sensitive and economical detection methods. Here we set out to engineer a previously identified OPP responsive transcription factor, ChpR, from Sinorhizobium melilotii to respond to alternative OPPs and generate a repertoire of whole-cell biosensors for OPPs. The ChpR transcription factor and cognate promoter P chpA, have been shown to activate transcription in the presence of the OPP chlorpyrifos (CPF). Utilizing a GFP reporter regulated by ChpR in a whole-cell biosensor we found that the system responds significantly better to 3,5,6-trichloro-2-pyridinol (TCP), the main degradation product of CPF, compared to CPF itself. This biosensor was able to respond to TCP at 390 nM within 4 h compared to 50 µM of CPF in 7 h. The ChpR-P chpA , and the activating ligand TCP, were able to regulate expression of a kanamycin resistance/sucrose sensitivity (kan/sacB) selection/counterselection module suitable for high throughput mutagenesis screening studies. The ability to control both GFP and the kan/sacB module demonstrates the utility of this reporter for the detection of CPF affected areas. The ChpR-P chpA system serves as an additional positive regulator switch to add to the growing repertoire of controllers available within synthetic biology.

2021 ◽  
Vol 22 (23) ◽  
pp. 13072
Ana S. Serras ◽  
Sérgio P. Camões ◽  
Bernardo Antunes ◽  
Vera M. Costa ◽  
Flávio Dionísio ◽  

Doxorubicin (Dox) is one of the most widely used treatments for breast cancer, although limited by the well-documented cardiotoxicity and other off-target effects. Mesenchymal stem cell (MSC) secretome has shown immunomodulatory and regenerative properties, further potentiated under 3D conditions. This work aimed to uncover the effect of the MSC-derived secretome from 3D (CM3D) or 2D (CM2D) cultures, in human malignant breast cells (MDA-MB-231), non-tumor breast epithelial cells (MCF10A) and differentiated AC16 cardiomyocytes, co-treated with Dox. A comprehensive proteomic analysis of CM3D/CM2D was also performed to unravel the underlying mechanism. CM3D/CM2D co-incubation with Dox revealed no significant differences in MDA-MB-231 viability when compared to Dox alone, whereas MCF10A and AC16 viability was consistently improved in Dox+CM3D-treated cells. Moreover, neither CM2D nor CM3D affected Dox anti-migratory and anti-invasive effects in MDA-MB-231. Notably, Ge-LC-MS/MS proteomic analysis revealed that CM3D displayed protective features that might be linked to the regulation of cell proliferation (CAPN1, CST1, LAMC2, RANBP3), migration (CCN3, MMP8, PDCD5), invasion (TIMP1/2), oxidative stress (COX6B1, AIFM1, CD9, GSR) and inflammation (CCN3, ANXA5, CDH13, GDF15). Overall, CM3D decreased Dox-induced cytotoxicity in non-tumor cells, without compromising Dox chemotherapeutic profile in malignant cells, suggesting its potential use as a chemotherapy adjuvant to reduce off-target side effects.

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5993
Bayley G. Matthews ◽  
Nikola A. Bowden ◽  
Michelle W. Wong-Brown

High-grade serous ovarian cancer (HGSOC) is the most common ovarian cancer subtype, and the overall survival rate has not improved in the last three decades. Currently, most patients develop recurrent disease within 3 years and succumb to the disease within 5 years. This is an important area of research, as the major obstacle to the treatment of HGSOC is the development of resistance to platinum chemotherapy. The cause of chemoresistance is still largely unknown and may be due to epigenetics modifications that are driving HGSOC metastasis and treatment resistance. The identification of epigenetic changes in chemoresistant HGSOC enables the development of epigenetic modulating drugs that may be used to improve outcomes. Several epigenetic modulating drugs have displayed promise as drug targets for HGSOC, such as demethylating agents azacitidine and decitabine. Others, such as histone deacetylase inhibitors and miRNA-targeting therapies, demonstrated promising preclinical results but resulted in off-target side effects in clinical trials. This article reviews the epigenetic modifications identified in chemoresistant HGSOC and clinical trials utilizing epigenetic therapies in HGSOC.

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 2061
Yan Zhang ◽  
Chenpeng Liu ◽  
Zhongmin Wan ◽  
Chen Yang ◽  
Shi Li ◽  

The design of bipolar plates is critical for improving the performance of proton exchange membrane fuel cells (PEMFCs). In this research, a new additional outlet based on a PEMFC’s parallel flow field was proposed, and three different positions of outlet were designed on the target side of gas flowing in parallel channels. The results revealed that the additional outlets are able to increase the gas speed through channels near the additional outlets, which results in a lower water saturation and a more uniform distribution of oxygen concentration at the interface between the catalyst layer (CL) and gas diffusion layer (GDL). With the variation of the outlet position in the target side, it was found that the additional outlet set in the middle of the target side exhibits the highest increase of peak power density, namely, 13%. Furthermore, the optimal position of the additional outlet was proved to be suitable for PEMFCs with various active surface areas, indicating the universality of the present results in the study.

2021 ◽  
Vol 1 ◽  
pp. 20-28
Nurista Dida Ayuningtyas ◽  
Agustina Putri Pitarisa ◽  
Silmi Mey Aryani

AbstractMahogany seed oil extract has pharmacological activities antimicrobial, antihypertensive, and anti-inflammatory. This potential can be developed into pharmaceutical dosage forms that are more practical to use. SNEDDS preparation is a dosage form that allows lipophilic active substances to be delivered to the target side of the drug. SNEDDS has oil, surfactant and co- surfactant components. In this study, the solubility of these components will be screened with mahogany seed oil extract. After finding the solubility of each component, the SNEDDS formula for mahogany seed oil extract was made. The oils used were oleic acid, VCO and IPM, cremophor surfactants RH40 and Tween 80, and co-surfactants PEG 400 and propylene glycol. The results of the solubility test were the largest components of SNEDDS, namely the components of oleic acid oil (98.4+0.00), cremophor RH40 (100.0+0.00), and PEG 400 (100.6+0.51). The SNEDDS formula for mahogany seed oil extract was made with a combination of oleic acid: cremophor RH40: PEG 400 1:8:1 with 200 L of extract. The characteristics of SNEDDS obtained are transmittance value of 98.83+0.06%, pH 5.8 + 0.24, and emulsification time of 34.33 + 6.66 seconds with grade A where SNEDDS quickly forms nanoemulsions in 1 minute, has a good appearance. clear.Keywords: Mahagonay, Solubility, SNEDDS, AbstrakEkstrak minyak biji mahoni memiliki aktifitas farmakologi yaitu antimikroba, antihipertensi, dan antiinflamasi. Potensi tersebut dapat dikembangkan ke dalam bentuk sediaan farmasi yang lebih praktis digunakan. Sediaan SNEDDS merupakan bentuk sediaan yang memungkinkan zat aktif yang bersifat lipofil untuk dihantarkan ke sisi target obat. SNEDDS memiliki komponen minyak, surfaktan dan ko surfaktan. Pada penelitian ini akan dilakukan screening kelarutan komponen tersebut dengan ekstrak minyak biji mahoni. Setelah ditemukan kelarutan masing- masing komponen kemudian dilakukan pembuatan formula SNEDDS ekstrak minyak biji mahoni. Minyak yang digunakan yaitu asam oleat, VCO dan IPM, surfaktan cremophor RH40 dan Tween 80, dan ko surfaktan PEG 400 dan propilenglikol. Hasil uji kelarutan paling besar komponen SNEDDS yaitu komponen minyak asam oleat (98.4+0.00), cremophor RH40 (100.0+0.00), dan PEG 400 (100.6+0.51). Formula SNEDDS ekstrak minyak biji mahoni dibuat dengan kombinasi asam oleat : cremophor RH40 : PEG 400 1:8:1 dengan ekstrak sebanyak 200 µL. Karakteristik SNEDDS yanng diperoleh nilai transmitan 98,83+0,06 %, pH 5,8 + 0,24, dan waktu emulsifikasi 34,33 + 6,66 detik dengan grade A dimana SNEDDS cepat membentuk nanoemulsi dalam 1 menit, memiliki penampilan yang jernih.Kata kunci: Kelarutan, Mahoni, SNEDDS,

2021 ◽  
Vol 22 (21) ◽  
pp. 11596
Miguel Hueso ◽  
Adrián Mallén ◽  
Marc Suñé-Pou ◽  
Josep M. Aran ◽  
Josep M. Suñé-Negre ◽  

Non-coding RNAs (ncRNAs) are emerging therapeutic tools but there are barriers to their translation to clinical practice. Key issues concern the specificity of the targets, the delivery of the molecules, and their stability, while avoiding “on-target” and “off-target” side effects. In this “ncRNA in therapeutics’’ issue, we collect several studies of the differential expression of ncRNAs in cardiovascular diseases, bone metabolism-related disorders, neurology, and oncology, and their potential to be used as biomarkers or therapeutic targets. Moreover, we review recent advances in the use of antisense ncRNAs in targeted therapies with a particular emphasis on their basic biological mechanisms, their translational potential, and future trends.

Vincent Vandeghinste

This article describes a hybrid approach to machine translation (MT) that is inspired by the rule-based, statistical, example-based, and other hybrid machine translation approaches currently used or described in academic literature. It describes how the approach was implemented for language pairs using only limited monolingual resources and hardly any parallel resources (the METIS-II system), and how it is currently implemented with rich resources on both the source and target side as well as rich parallel data (the PaCo-MT system). We aim to illustrate that a similar paradigm can be used, irrespectively of the resources available, but of course with an impact on translation quality.

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