A considerable proportion of patients with rheumatoid arthritis (RA) do not respond to monospecific agents. The purpose of our study was to generate a hybrid form of biologics, targeting tumor-necrosis factor alpha (TNFα) and interleukin-6 receptor (IL-6R), and determine its anti-arthritic properties in vitro and in vivo. A novel dual target-directed agent (DTA(A7/sTNFR2)) was generated by conj...

The electrical conductivities and plausible charge-ordering states in the room temperature (r.t.) phase for MMX chains [Ni(2)(dta)(4)I](∞) and [Pt(2)(dta)(4)I](∞) (dta = CH(3)CS(2)(-)) have been analyzed with periodic density functional theory (DFT) and correlated ab initio calculations combined with the effective Hamiltonian theory. Periodic DFT calculations show a more delocalized nature of t...

Depression and anxiety involve hippocampal dysfunction, but the specific relationship between these mood disorders and adult hippocampal dentate gyrus neurogenesis remains unclear. In both humans with MDD and rodent models of depression, administration of antidepressants increases DG progenitor and granule cell number, yet rodents with induced ablation of DG neurogenesis typically do not demons...

Transportation practice is increasingly recognizing the need for dynamic models for realistic scenario analyses and policy decision-making. Dynamic Traffic Assignment (DTA) theory and tools are now thought to be sufficiently advanced to meet this need. However, DTA has historically been associated with mesoscopic models, motivated by the perceived computational intractability of high-fidelity m...

BACKGROUND Posterior glenoid bone deficiency in the setting of posterior glenohumeral instability is typically addressed with bone block augmentation with iliac crest bone grafts (ICBGs). Reconstruction with fresh distal tibial allograft (DTA) is an alternative option, with the theoretical advantages of restoring the glenoid articular surface, improving joint congruity, and providing the biolog...

This paper makes verifying continuous-time Markov chains (CTMCs) against deterministic timed automata (DTA) objectives practical. We show that verifying 1-clock DTA can be done by analyzing subgraphs of the product of CTMC C and the region graph of DTA A. This improves upon earlier results and allows to only use standard analysis algorithms. Our graph decomposition approach naturally enables bi...

The increased understanding of immunoregulatory receptor pathways is now offering promising opportunities for immunotherapeutic intervention, as exemplified by the success of anti-CTLA-4 antibody (Ab) Ipilimumab. More recently, an agonist Ab for the co-stimulatory receptor glucocorticoid-induced TNF receptor (GITR) has entered the clinical evaluation. Preclinical studies have well documented th...

BACKGROUND Dementia includes a group of neurodegenerative disorders characterized by progressive loss of cognitive function and a decrease in the ability to perform activities of daily living. Systematic reviews of diagnostic test accuracy (DTA) focus on how well the index test detects patients with the disease in terms of figures such as sensitivity and specificity. Although DTA reviews about ...

This paper considers the verification of continuous-time Markov decision process (CTMDPs) against single-clock deterministic timed automata (DTA) specifications. The central issue is to compute the maximum probability of the set of timed paths of a CTMDP C that are accepted by a DTA A. We show that this problem can be reduced to a linear programming problem whose coefficients are maximum timed ...

We address the issue of efficiently automating assume-guarantee reasoning for simulation conformance between finite state systems and specifications. We focus on a non-circular assume-guarantee proof rule, and show that there is a weakest assumption that can be represented canonically by a deterministic tree automata (DTA). We then present an algorithm L that learns this DTA automatically in an...