Engineering DNA Nanostructures to Manipulate Immune Receptor Signaling and Immune Cell Fates.

Immune cells sense, communicate, and logically integrate a multitude of environmental signals to make important cell-fate decisions and fulfill their effector functions. These processes are initiated and regulated by a diverse array of immune receptors and via their dynamic spatiotemporal organization upon ligand binding. Given the widespread relevance of the immune system to health and disease, there have been significant efforts toward understanding the biophysical principles governing immune receptor signaling and activation, as well as the development of biomaterials which exploit these principles for therapeutic immune engineering. Here, how advances in the field of DNA nanotechnology constitute a growing toolbox for further pursuit of these endeavors is discussed. Key cellular players involved in the induction of immunity against pathogens or diseased cells are first summarized. How the ability to design DNA nanostructures with custom shapes, dynamics, and with site-specific incorporation of diverse guests can be leveraged to manipulate the signaling pathways that regulate these processes is then presented. It is followed by highlighting emerging applications of DNA nanotechnology at the crossroads of immune engineering, such as in vitro reconstitution platforms, vaccines, and adjuvant delivery systems. Finally, outstanding questions that remain for further advancing immune-modulatory DNA nanodevices are outlined.

Discriminative functions and over-training as class-enhancing determinants of meaningful stimuli.

Likelihood of equivalence class formation (yield) was influenced by pre-class formation of simultaneous and successive discriminations, their mastery criteria, and overtraining of the successive discriminations. Each undergraduate in seven groups attempted to form two 3-node, 5-member equivalence classes (ABCDE). In the pictorial (PIC) group, meaningless nonsense syllables were used as the A, B, D, and E stimuli and meaningful pictures as the C stimuli. Nonsense syllables only were used in the other groups. The abstract (ABS) or 0-0-0 group involved no pre-class training. In the 84-0-0, 84-5-0 and 84-20-0 groups, simultaneous discriminations were trained among C stimuli to a mastery criterion of 84 trials, followed by successive discriminations trained to mastery criteria of 0, 5, and 20 trials, respectively. In the 84-20-0, 84-20-100, and 84-20-500 groups, simultaneous and successive discriminations were trained as noted, followed by overtraining with 0, 100, 500 successive-discrimination trials, respectively. The ABS group produced a 6% yield with the 84-0-0, 84-5-0, and 84-20-0 groups producing further modest increments. Overtraining produced a linear increase in yield, reaching 85% after 500 overtraining trials, a yield matching that produced by classes containing pictures as C stimuli (PIC). Thus, acquired discriminative functions and the overtraining of at least one function can account for class enhancement by meaningful stimuli.

Using behavioural skills training to treat aggression in adults with mild intellectual disability in a forensic setting.

BACKGROUND: Previous studies of anger management in people with intellectual disability failed to control for the effects of the number of provocative stimuli presented and lacked direct measures of behaviour and treatment integrity data. METHODS: This experiment systematically assessed and presented discriminative stimuli for aggressive behaviour, taught alternative behaviour in response to discriminative stimuli for aggressive behaviour and used behavioural skills training with three adults with mild intellectual disability. RESULTS: Following behavioural skills training, the adult's percentage of aggressive responses declined and replacement responses increased in response to provocative stimuli. Treatment gains generalized to novel antecedent events, novel staff and novel settings and were socially valid. After intervention, community trips increased for all three participants. CONCLUSIONS: Behavioural skills training to teach alternate behaviour to aggression with carefully planned procedures to promote generalization caused a socially valid increase in alternate behaviour and a socially valid decrease in aggression.

Functional analysis and treatment of the delusional statements of a man with multiple disabilities: a four-year follow-up.

Although delusional statements in people with intellectual disabilities and traumatic brain injury can be treated using behavioral interventions, none have demonstrated long-term treatment effects. In the current study, a functional analysis demonstrated that delusional statements were maintained by attention. Differential reinforcement of alternative behavior and extinction of delusional statements resulted in near elimination of delusional statements and an increase in nondelusional statements. Follow-up at 6 months, 1, 2, and 4 years indicated that treatment gains were maintained with continued staff training.

Equivalence class formation: a method for teaching statistical interactions.

Many students struggle with statistical concepts such as interaction. In an experimental group, participants took a paper-and-pencil test and then were given training to establish equivalent classes containing four different statistical interactions. All participants formed the equivalence classes and showed maintenance when probes contained novel negative exemplars. Thereafter, participants took a second paper-and-pencil test. Participants in the control group received two versions of the paper-and-pencil test without equivalence-based instruction. All participants in the experimental group showed increased paper-and-pencil test scores after forming the interaction-indicative equivalence classes. Class-indicative responding also generalized to novel exemplars and the novel question format used in the paper-and-pencil test. Test scores did not change with repetition for control group participants. Implications for behavioral diagnostics and teaching technology are discussed.