Primacy biases endure the addition of frequency variability.

The primacy bias (PB) is a phenomenon that indicates the brain does not always process sensory information as an 'ideal Bayesian observer', but rather is disproportionately influenced by first impressions. This study was designed to establish whether a PB observed in auditory event-related potentials (ERPs) to a sequence of sound remained evident in the presence of increased levels of tone frequency variation. Two groups of participants were presented with a novel oddball paradigm, while simultaneously having cortical activity recorded with an EEG. In the control group, participants heard a two-tone sequence where the probability of the two tones of different duration switched after 480 sounds/2.4 min block, so that the tone initially encountered as rare became common and vice versa. The key manipulation introduced in the test group was a change of frequency in each block, removing a key element of regularity. The additional frequency variation resulted in no significant difference in the PB between the groups. The data suggest powerful first learning effects are not disrupted by frequency changes, indicating the robustness of learning heuristics.

Lessons learned from the pilot study of an orthostatic hypotension intervention in the subacute phase following spinal cord injury.

Context: Following spinal cord injury (SCI) at the cervical or upper-thoracic level, orthostatic hypotension (OH) is observed in 13-100% of patients. This study aimed to test the feasibility of conducting a randomized controlled trial combining a dynamic tilt-table (Erigo®) and functional electrical stimulation (FES) to mitigate OH symptoms in the subacute phase after SCI. Design: Pilot study. Setting: A tertiary rehabilitation hospital. Participants: Inpatients who had a C4-T6 SCI (AIS A-D) less than 12 weeks before recruitment, and reported symptoms of OH in their medical chart. Interventions: Screening sit-up test to determine eligibility, then 1 assessment session and 3 intervention sessions with Erigo® and FES for eligible participants. Outcome measures: Recruitment rate, duration of assessment and interventions, resources used, blood pressure, and Calgary Presyncope Form (OH symptoms). Results: Amongst the 232 admissions, 148 inpatient charts were reviewed, 11 inpatients met all inclusion criteria, 7 participated in a screening sit-up test, and 2 exhibited OH. Neither of the two participants recruited in the pilot study was able to fully complete the assessment and intervention sessions due to scheduling issues (i.e. limited available time). Conclusion: This pilot study evidenced the non-feasibility of the clinical trial as originally designed, due to the low recruitment rate and the lack of available time for research in participant's weekday schedule. OH in the subacute phase after SCI was less prevalent and less incapacitating than expected. Conventional management and spontaneous resolution of symptoms appeared sufficient to mitigate OH in most patients with subacute SCI.

Biochemical characterization of a uranyl ion-specific DNAzyme.

Uranyl ion-specific DNAzyme: A DNAzyme (lower strand) cleaves the substrate (upper strand) in the presence of the uranyl ion. The enzyme folds into a bulged three-way-junction structure with catalytically important nucleotides residing in the bulge. A highly conserved GA mismatch is also crucial for the enzyme's activity.The biochemical characterization of a DNAzyme that is highly specific for uranyl (UO(2) (2+)) ions is described. Sequence alignment, enzyme truncation, and mutation studies have resulted in a conserved sequence that folds into a bulged stem-loop structure. Interestingly, a GA pair next to the scissile site is important for the uranyl ion-specific DNAzyme; this is reminiscent of the GT wobble base pair adjacent to the cleavage site that is crucial for the Pb(II)-specific 8-17 DNAzyme activity. Therefore wobble pairs might be important for formation of metal-specific metal-binding sites in DNAzymes. The DNAzyme binds the uranyl ion with a dissociation constant of 469 nM, which is among the strongest metal-binding affinities in nucleic acid enzymes reported to date. This explains why a catalytic beacon fluorescent sensor based on this enzyme has a detection limit (45 pM) that rivals the most-sensitive analytical instrument. It also has over 1 000 000-fold specificity for the uranyl ion over other metal ions. The DNAzyme can carry out multiple turnover reactions that follow the Michaelis-Menten equation, with a k(cat) of 1.46 min(-1) and a K(M) of 463 nM, similar to that of the 8-17 DNAzyme. The pH profile shows a bell-shaped curve that reaches a maximum at pH 5.5, at which the in vitro selection was carried out; this suggests that in vitro selection can be performed to obtain DNAzymes with optimal performance under specific conditions under which practical applications are required. These findings enrich our fundamental understanding of metal-binding sites in nucleic acids and allow the design of sensors with better performance.

A catalytic beacon sensor for uranium with parts-per-trillion sensitivity and millionfold selectivity.

Here, we report a catalytic beacon sensor for uranyl (UO2(2+)) based on an in vitro-selected UO2(2+)-specific DNAzyme. The sensor consists of a DNA enzyme strand with a 3' quencher and a DNA substrate with a ribonucleotide adenosine (rA) in the middle and a fluorophore and a quencher at the 5' and 3' ends, respectively. The presence of UO2(2+) causes catalytic cleavage of the DNA substrate strand at the rA position and release of the fluorophore and thus dramatic increase of fluorescence intensity. The sensor has a detection limit of 11 parts per trillion (45 pM), a dynamic range up to 400 nM, and selectivity of >1-million-fold over other metal ions. The most interfering metal ion, Th(IV), interacts with the fluorescein fluorophore, causing slightly enhanced fluorescence intensity, with an apparent dissociation constant of approximately 230 microM. This sensor rivals the most sensitive analytical instruments for uranium detection, and its application in detecting uranium in contaminated soil samples is also demonstrated. This work shows that simple, cost-effective, and portable metal sensors can be obtained with similar sensitivity and selectivity as much more expensive and sophisticated analytical instruments. Such a sensor will play an important role in environmental remediation of radionuclides such as uranium.