The formal analysis of domain-independent planning has been largely influenced by David Chapman's system Tweak, built upon a modal truth criterion (MTC), which is proved correct and complete. However, D. Chapman ends his work arguing without any formal proof that the white knight technique used in his MTC is “pretty useless” (a fact informally accepted in the planning community). Here, it is fo...

Mutations in the TNF family of proteins have been associated with inherited forms of immune deficiency. Using an array-based sequencing assay, we identified an autosomal-dominant deficiency in TNF-like weak inducer of apoptosis (TWEAK; TNFSF12) in a kindred with recurrent infection and impaired antibody responses to protein and polysaccharide vaccines. This mutation occurs in the sixth exon of ...

PURPOSE Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible molecule 14 (Fn14) are a ligand-receptor pair frequently overexpressed in solid tumors. TWEAK Fn14 signaling regulates multiple oncogenic processes through MAPK, AKT, and NFκB pathway activation. A phase I study of RG7212, a humanized anti-TWEAK IgG1κ monoclonal antibody, was cond...

Fibroblast growth factor (FGF)-inducible 14 (Fn14) activates the classical and alternative NFκB (nuclear ‘kappa-light-chain-enhancer’ of activated B-cells) signaling pathway but also enhances tumor necrosis (TNF)-induced cell death. Fn14 expression is upregulated in non-hematopoietic cells during tissue injury often highly expressed solid cancers. In view latter, there were are considerable pre...

There are no pathophysiolgical therapeutic approaches to acute kidney injury (AKI) and the mortality remains high. In addition chronic kidney disease (CKD) predisposes to AKI and AKI contributes to progression of CKD. Recently a transcriptomics approach unveiled a relationship between AKI, inflammation and the regulation of ageing. A transcriptomics analysis of experimental AKI revealed increas...

The tumor necrosis factor (TNF) superfamily member TNF-like weak inducer of apoptosis (TWEAK) was initially described in a 1997 publication co-authored by investigators from the biotechnology company Biogen (now Biogen-Idec) and the University of Geneva. Four years later, researchers at the biotechnology company Immunex (now part of Amgen) reported the cloning and characterization of the human ...

Purpose: The role and function of a novel human AlkB homologue, ALKBH3, in human urothelial carcinoma development were examined. Experimental design: Biologic roles of ALKBH3 were examined by gene silencing analysis using in vitro and in vivo siRNA transfection. Immunohistochemical analyses of ALKBH3 and the relatedmolecules using human bladder cancer samples were conducted to estimate the asso...

Tumor necrosis factor (TNF) has been firmly established as a pathogenic factor in heart failure, a significant socio-economic burden. In this review, we will explore the role of other members of the TNF/TNF receptor superfamily (TNFSF/TNFRSF) in cardiovascular diseases (CVDs) focusing on TWEAK and its receptor Fn14, new players in myocardial remodeling and heart failure. The TWEAK/Fn14 pathway ...

When I first developed an Addiction course for the Honors College at UMass-Boston in 2006, it focused exclusively on the acute and long-term effects of psychoactive substances on the brain. However, I soon realized that a strictly biological perspective failed to capture how this complex disorder affected the whole person. Students had no insight into addicts' thoughts, feelings, behaviors or h...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) demonstrates specific anti-cancer activity, but insufficient efficacy in patients. A fusion protein Fn14·TRAIL, that combines soluble TRAIL molecule with a specific TWEAK receptor Fn14, is a better apoptosis-inducer for hepatocellular carcinomas than soluble TRAIL. However, Fn14·TRAIL does not effectively induce apoptosis in tumors...