Donor-Acceptor Oligorotaxanes Made to Order

Five donor–acceptor oligorotaxanes made up of dumbbells composed of tetraethylene glycol chains, interspersed with three and five 1,5-dioxynaphthalene units, and terminated by 2,6-diisopropylphenoxy stoppers, have been prepared by the threading of discrete numbers of cyclobis(paraquat-p-phenylene) rings, followed by a kinetically controlled stoppering protocol that relies on click chemistry. The well-known copper(I)-catalyzed alkyne–azide cycloaddition between azide functions placed at the ends of the polyether chains and alkyne-bearing stopper precursors was employed during the final kinetically controlled template-directed synthesis of the five oligorotaxanes, which were characterized subsequently by ^1H NMR spectroscopy at low temperature (233 K) in deuterated acetonitrile. The secondary structures, as well as the conformations, of the five oligorotaxanes were unraveled by spectroscopic comparison with the dumbbell and ring components. By focusing attention on the changes in chemical shifts of some key probe protons, obtained from a wide range of low-temperature spectra, a picture emerges of a high degree of folding within the thread protons of the dumbbells of four of the five oligorotaxanes—the fifth oligorotaxane represents a control compound in effect— brought about by a combination of C-H···O and π–π stacking interactions between the p-electron-deficient bipyridinium units in the rings and the π-electron-rich 1,5-dioxynaphthalene units and polyether chains in the dumbbells. The secondary structures of a foldamer-like nature have received further support from a solid-state superstructure of a related [3]pseudorotaxane and density functional calculations performed thereon

A Push-Button Molecular Switch

The preparation, characterization, and switching mechanism of a unique single-station mechanically switchable hetero[2]catenane are reported. The facile synthesis utilizing a “threading-followed-by-clipping” protocol features Cu^(2+)-catalyzed Eglinton coupling as a mild and efficient route to the tetrathiafulvalene-based catenane in high yield. The resulting mechanically interlocked molecule operates as a perfect molecular switch, most readily described as a “push-button” switch, whereby two discrete and fully occupied translational states are toggled electrochemically at incredibly high rates. This mechanical switching was probed using a wide variety of experimental techniques as well as quantum-mechanical investigations. The fundamental distinctions between this single-station [2]catenane and other more traditional bi- and multistation molecular switches are significant

Reduction of freezing of gait in Parkinson's disease by repetitive robot-assisted treadmill training: a pilot study

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease is a chronic, neurodegenerative disease characterized by gait abnormalities. Freezing of gait (FOG), an episodic inability to generate effective stepping, is reported as one of the most disabling and distressing parkinsonian symptoms. While there are no specific therapies to treat FOG, some external physical cues may alleviate these types of motor disruptions. The purpose of this study was to examine the potential effect of continuous physical cueing using robot-assisted sensorimotor gait training on reducing FOG episodes and improving gait.</p> <p>Methods</p> <p>Four individuals with Parkinson's disease and FOG symptoms received ten 30-minute sessions of robot-assisted gait training (Lokomat) to facilitate repetitive, rhythmic, and alternating bilateral lower extremity movements. Outcomes included the FOG-Questionnaire, a clinician-rated video FOG score, spatiotemporal measures of gait, and the Parkinson's Disease Questionnaire-39 quality of life measure.</p> <p>Results</p> <p>All participants showed a reduction in FOG both by self-report and clinician-rated scoring upon completion of training. Improvements were also observed in gait velocity, stride length, rhythmicity, and coordination.</p> <p>Conclusions</p> <p>This pilot study suggests that robot-assisted gait training may be a feasible and effective method of reducing FOG and improving gait. Videotaped scoring of FOG has the potential advantage of providing additional data to complement FOG self-report.</p

Mechanically Stabilized Tetrathiafulvalene Radical Dimers

Two donor−acceptor [3]catenanes—composed of a tetracationic molecular square, cyclobis(paraquat-4,4′-biphenylene), as the π-electron deficient ring and either two tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) containing macrocycles or two TTF-butadiyne-containing macrocycles as the π-electron rich components—have been investigated in order to study their ability to form TTF radical dimers. It has been proven that the mechanically interlocked nature of the [3]catenanes facilitates the formation of the TTF radical dimers under redox control, allowing an investigation to be performed on these intermolecular interactions in a so-called “molecular flask” under ambient conditions in considerable detail. In addition, it has also been shown that the stability of the TTF radical-cation dimers can be tuned by varying the secondary binding motifs in the [3]catenanes. By replacing the DNP station with a butadiyne group, the distribution of the TTF radical-cation dimer can be changed from 60% to 100%. These findings have been established by several techniques including cyclic voltammetry, spectroelectrochemistry and UV−vis−NIR and EPR spectroscopies, as well as with X-ray diffraction analysis which has provided a range of solid-state crystal structures. The experimental data are also supported by high-level DFT calculations. The results contribute significantly to our fundamental understanding of the interactions within the TTF radical dimers

The spectrum of BPS branes on a noncompact Calabi-Yau

We begin the study of the spectrum of BPS branes and its variation on lines of marginal stability on O_P^2(-3), a Calabi-Yau ALE space asymptotic to C^3/Z_3. We show how to get the complete spectrum near the large volume limit and near the orbifold point, and find a striking similarity between the descriptions of holomorphic bundles and BPS branes in these two limits. We use these results to develop a general picture of the spectrum. We also suggest a generalization of some of the ideas to the quintic Calabi-Yau.Comment: harvmac, 45 pp. (v2: added references

Solutions of the Strominger System via Stable Bundles on Calabi-Yau Threefolds

We prove that a given Calabi-Yau threefold with a stable holomorphic vector bundle can be perturbed to a solution of the Strominger system provided that the second Chern class of the vector bundle is equal to the second Chern class of the tangent bundle. If the Calabi-Yau threefold has strict SU(3) holonomy then the equations of motion derived from the heterotic string effective action are also satisfied by the solutions we obtain.Comment: 19 pages, late

The effects of test-enhanced learning on long-term retention in AAN annual meeting courses.

OBJECTIVE: We measured the long-term retention of knowledge gained through selected American Academy of Neurology annual meeting courses and compared the effects of repeated quizzing (known as test-enhanced learning) and repeated studying on that retention. METHODS: Participants were recruited from 4 annual meeting courses. All participants took a pretest. This randomized, controlled trial utilized a within-subjects design in which each participant experienced 3 different postcourse activities with each activity performed on different material. Each key information point from the course was randomized in a counterbalanced fashion among participants to one of the 3 activities: repeated short-answer quizzing, repeated studying, and no further exposure to the materials. A final test covering all information points from the course was taken 5.5 months after the course. RESULTS: Thirty-five participants across the 4 courses completed the study. Average score on the pretest was 36%. Performance on the final test showed that repeated quizzing led to significantly greater long-term retention relative to both repeated studying (55% vs 46%; t[34] = 3.28, SEM = 0.03, p = 0.01, d = 0.49) and no further exposure (55% vs 44%; t[34] = 3.16, SEM = 0.03, p = 0.01, d = 0.58). Relative to the pretest baseline, repeated quizzing helped participants to retain almost twice as much of the knowledge acquired from the course compared to repeated studying or no further exposure. CONCLUSIONS: Whereas annual meeting continuing medical education (CME) courses lead to long-term gains in knowledge, when repeated quizzing is added, retention is significantly increased. CME planners may consider adding repeated quizzing to increase the impact of their courses

The contribution of nonrigid motion and shape information to object perception in pigeons and humans

The ability to perceive and recognize objects is essential to many animals, including humans. Until recently, models of object recognition have primarily focused on static cues, such as shape, but more recent research is beginning to show that motion plays an important role in object perception. Most studies have focused on rigid motion, a type of motion most often associated with inanimate objects. In contrast, nonrigid motion is often associated with biological motion and is therefore ecologically important to visually dependent animals. In this study, we examined the relative contribution of nonrigid motion and shape to object perception in humans and pigeons, two species that rely extensively on vision. Using a parametric morphing technique to systematically vary nonrigid motion and three-dimensional shape information, we found that both humans and pigeons were able to rely solely on either shape or nonrigid motion information to identify complex objects when one of the two cues was degraded. Humans and pigeons also showed similar 80% accuracy thresholds when the information from both shape and motion cues were degraded. We argue that the use of nonrigid motion for object perception is evolutionarily important and should be considered in general theories of vision at least with respect to visually sophisticated animals

Primary Care Access for new Patients on the eve of Health Care Reform

Importance: Current measures of access to care have intrinsic limitations and may not accurately reflect the capacity of the primary care system to absorb new patients. Objective: To assess primary care appointment availability by state and insurance status. Design, Setting, and Particpants: We conducted a simulated patient study. Trained field staff, randomly assigned to private insurance, Medicaid, or uninsured, called primary care offices requesting the first available appointment for either routine care or an urgent health concern. The study included a stratified random sample of primary care practices treating nonelderly adults within each of 10 states (Arkansas, Georgia, Illinois, Iowa, Massachusetts, Montana, New Jersey, Oregon, Pennsylvania, and Texas), selected for diversity along numerous dimensions. Collectively, these states comprise almost one-third of the US nonelderly, Medicaid, and currently uninsured populations. Sampling was based on enrollment by insurance type by county. Analyses were weighted to obtain population-based estimates for each state. Main Outcomes and Measures: The ability to schedule an appointment and number of days to the appointment. We also examined cost and payment required at the visit for the uninsured. Results: Between November 13, 2012, and April 4, 2013, we made 12,907 calls to 7788 primary care practices requesting new patient appointments. Across the 10 states, 84.7% (95% CI, 82.6%-86.8%) of privately insured and 57.9% (95% CI, 54.8%-61.0%) of Medicaid callers received an appointment. Appointment rates were 78.8% (95% CI, 75.6%-82.0%) for uninsured patients with full cash payment but only 15.4% (95% CI, 13.2%-17.6%) if payment required at the time of the visit was restricted to $75 or less. Conditional on getting an appointment, median wait times were typically less than 1 week (2 weeks in Massachusetts), with no differences by insurance status or urgency of health concern. Conclusions and Relevance: Although most primary care physicians are accepting new patients, access varies widely across states and insurance status. Navigator programs are needed, not only to help patients enroll but also to identify practices accepting new patients within each plan\u27s network. Tracking new patient appointment availability over time can inform policies designed to strengthen primary care capacity and enhance the effectiveness of the coverage expansions with the Patient Protection and Affordable Care Act