Abstract. Aiming to build a complete benchmark for better evaluation of existing ontology systems, we extend the well-known Lehigh University Benchmark in terms of inference and scalability testing. The extended benchmark, named University Ontology Benchmark (UOBM), includes both OWL Lite and OWL DL ontologies covering a complete set of OWL Lite and DL constructs, respectively. We also add necessary properties to construct effective instance links and improve instance generation methods to make the scalability testing more convincing. Several well-known ontology systems are evaluated on the extended benchmark and detailed discussions on both existing ontology systems and future benchmark development are presented.

Human mesenchymal stem cells (hMSCs) are multipotent cells, which exhibit plastic adherence, express specific cell surface marker spectrum, and have multi-lineage differentiation potential. These cells can be obtained from multiple tissues. Dental tissue-derived hMSCs (dental MSCs) possess the ability to give rise to mesodermal lineage (osteocytes, adipocytes, and chondrocytes), ectodermal lineage (neurocytes), and endodermal lineages (hepatocytes). Dental MSCs were first isolated from dental pulp of the extracted third molar and till now they have been purified from various dental tissues, including pulp tissue of permanent teeth and exfoliated deciduous teeth, apical papilla, periodontal ligament, gingiva, dental follicle, tooth germ, and alveolar bone. Dental MSCs are not only easily accessible but are also expandable in vitro with relative genomic stability for a long period of time. Moreover, dental MSCs have exhibited immunomodulatory properties by secreting cytokines. Easy accessibility, multi-lineage differentiation potential, and immunomodulatory effects make dental MSCs distinct from the other hMSCs and an effective tool in stem cell-based therapy. Several preclinical studies and clinical trials have been performed using dental MSCs in the treatment of multiple ailments, ranging from dental diseases to nondental diseases. The present review has summarized dental MSC sources, multi-lineage differentiation capacities, immunomodulatory features, its potential in the treatment of diseases, and its application in both preclinical studies and clinical trials. The regenerative therapeutic strategies in dental medicine have also been discussed.

Mechanisms to maintain genomic integrity are essential for cells to remain viable. Not surprisingly, disruption of key DNA damage response pathway factors, such as ataxia telangiectasiamutated (ATM)/ataxia telangiectasia and RAD3-related (ATR) results in loss of genomic integrity. Here, a synthetic lethal siRNA-screening approach not only confirmed ATM but identified additional replication checkpoint proteins, when ablated, enhanced ATR inhibitor (ATRi) response in a high-content g-H2AX assay. Cancers with inactivating ATM mutations exhibit impaired DNA double-stranded break (DSB) repair and rely on compensatory repair pathways for survival. Therefore, impairing ATR activity may selectively sensitize cancer cells to killing. ATR inhibition in an ATM-deficient context results in phosphorylation of DNA-dependent protein kinase catalytic subunits (DNAPKcs) and leads to induction of g-H2AX. Using both in vitro and in vivo models, ATR inhibition enhanced efficacy in ATM loss-offunction mantle cell lymphoma (MCL) compared with ATM wildtype cancer cells. In summary, single-agent ATR inhibitors have therapeutic utility in the treatment of cancers, like MCL, in which ATM function has been lost.Implications: These data suggest that single-agent ATR inhibitors have therapeutic utility and that ATR uses a complex and coordinated set of proteins to maintain genomic stability that could be further exploited.

The nucleoside adenosine is a potent regulator of vascular homeostasis, but it remains unclear how expression or function of the adenosine‐metabolizing enzyme adenosine kinase (ADK) and the intracellular adenosine levels influence angiogenesis. We show here that hypoxia lowered the expression of ADK and increased the levels of intracellular adenosine in human endothelial cells. Knockdown (KD) of ADK elevated intracellular adenosine, promoted proliferation, migration, and angiogenic sprouting in human endothelial cells. Additionally, mice deficient in endothelial ADK displayed increased angiogenesis as evidenced by the rapid development of the retinal and hindbrain vasculature, increased healing of skin wounds, and prompt recovery of arterial blood flow in the ischemic hindlimb. Mechanistically, hypomethylation of the promoters of a series of pro‐angiogenic genes, especially for VEGFR2 in ADK KD cells, was demonstrated by the Infinium methylation assay. Methylation‐specific PCR, bisulfite sequencing, and methylated DNA immunoprecipitation further confirmed hypomethylation in the promoter region of VEGFR2 in ADK‐deficient endothelial cells. Accordingly, loss or inactivation of ADK increased VEGFR2 expression and signaling in endothelial cells. Based on these findings, we propose that ADK downregulation‐induced elevation of intracellular adenosine levels in endothelial cells in the setting of hypoxia is one of the crucial intrinsic mechanisms that promote angiogenesis.

Antibody dependent enhancement (ADE) of dengue virus (DENV) infection is identified as the main risk factor of severe Dengue diseases. Through opsonization by subneutralizing or non-neutralizing antibodies, DENV infection suppresses innate cell immunity to facilitate viral replication. However, it is largely unknown whether suppression of type-I IFN is necessary for a successful ADE infection. Here, we report that both DENV and DENV-ADE infection induce an early ISG (NOS2) expression through RLR-MAVS signalling axis independent of the IFNs signaling. Besides, DENV-ADE suppress this early antiviral response through increased autophagy formation rather than induction of IL-10 secretion. The early induced autophagic proteins ATG5-ATG12 participate in suppression of MAVS mediated ISGs induction. Our findings suggest a mechanism for DENV to evade the early antiviral response before IFN signalling activation. Altogether, these results add knowledge about the complexity of ADE infection and contribute further to research on therapeutic strategies.