Seconds-scale coherence in a tweezer-array optical clock

Optical clocks based on atoms and ions achieve exceptional precision and accuracy, with applications to relativistic geodesy, tests of relativity, and searches for dark matter. Achieving such performance requires balancing competing desirable features, including a high particle number, isolation of atoms from collisions, insensitivity to motional effects, and high duty-cycle operation. Here we demonstrate a new platform based on arrays of ultracold strontium atoms confined within optical tweezers that realizes a novel combination of these features by providing a scalable platform for isolated atoms that can be interrogated multiple times. With this tweezer-array clock, we achieve greater than 3 second coherence times and record duty cycles up to 96%, as well as stability commensurate with leading platforms. By using optical tweezer arrays --- a proven platform for the controlled creation of entanglement through microscopic control --- this work further promises a new path toward combining entanglement enhanced sensitivities with the most precise optical clock transitions

No Evidence for a Cumulative Impact Effect on Concussion Injury Threshold

Recent studies using a helmet-based accelerometer system (Head Impact Telemetry System [HITS]) have demonstrated that concussions result from a wide range of head impact magnitudes. Variability in concussion thresholds has been proposed to result from the cumulative effect of non-concussive head impacts prior to injury. We used the HITS to collect biomechanical data representing >100,000 head impacts in 95 high school football players over 4 years. The cumulative impact histories prior to 20 concussive impacts in 19 athletes were compared to the cumulative impact histories prior to the three largest magnitude non-concussive head impacts in the same athletes. No differences were present in any impact history variable between the concussive and non-concussive high magnitude impacts. These analyses included the number of head impacts, cumulative HIT severity profile value, cumulative linear acceleration, and cumulative rotational acceleration during the same practice or game session, as well as over the 30-min and 1 week preceding these impacts. Our data do not support the proposal that impact volume or intensity influence concussion threshold in high school football athletes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90490/1/neu-2E2011-2E1910.pd

Syndromic features and mild cognitive impairment in mice with genetic reduction on p300 activity: Differential contribution of p300 and CBP to Rubinstein-Taybi syndrome etiology

Rubinstein-Taybi syndrome (RSTS) is a complex autosomal-dominant disease characterized by mental and growth retardation and skeletal abnormalities. A majority of the individuals diagnosed with RSTS carry heterozygous mutation in the gene CREBBP, but a small percentage of cases are caused by mutations in EP300. To investigate the contribution of p300 to RSTS pathoetiology, we carried out a comprehensive and multidisciplinary characterization of p300+/- mice. These mice exhibited facial abnormalities and impaired growth, two traits associated to RSTS in humans. We also observed abnormal gait, reduced swimming speed, enhanced anxiety in the elevated plus maze, and mild cognitive impairment during the transfer task in the water maze. These analyses demonstrate that p300+/- mice exhibit phenotypes that are reminiscent of neurological traits observed in RSTS patients, but their comparison with previous studies on CBP deficient strains also indicates that, in agreement with the most recent findings in human patients, the activity of p300 in cognition is likely less relevant or more susceptible to compensation than the activity of CBP. © 2009 Elsevier Inc. All rights reserved.This work was supported by the European Commission grant MEXT-CT-2003-509550, the Spanish Ministry of Science and Innovation Grants CSD2007-00023 and SAF2008-00611, and a grant from Fundación Ramón Areces. J.V. holds a fellowship from the Generalitat Valenciana and J.P.L.-A. a Juan de la Cierva contract supported by the Spanish Ministry of Science and Innovation.Peer Reviewe

Post-Concussion Cognitive Declines and Symptomatology Are Not Related to Concussion Biomechanics in High School Football Players

Concussion is a major public health concern with nearly 4 million injuries occurring each year in the United States. In the acute post-injury stage, concussed individuals demonstrate cognitive function and motor control declines as well as reporting increased symptoms. Researchers have hypothesized that the severity of these impairments is related to impact magnitude. Using the Head Impact Telemetry System (HITS) to record head impact biomechanics, we sought to correlate pre- and post-concussive impact characteristics with declines in cognitive performance and increases in concussion-related symptoms. Over four seasons, 19 high school football athletes wearing instrumented helmets sustained 20 diagnosed concussions. Each athlete completed a baseline computer-based symptom and cognitive assessment during the pre-season and a post-injury assessment within 24-h of injury. Correlational analyses identified no significant relationships between symptoms and cognitive performance change scores and impact biomechanics (i.e., time from session start until injury, time from the previous impact, peak linear acceleration, peak rotational acceleration, and HIT severity profile [HITsp]). Nor were there any significant relationships between change scores and the number of impacts, cumulative linear acceleration, cumulative rotational acceleration, or cumulative HITsp values associated with all impacts prior to or following the injury. This investigation is the first to examine the relationship between concussion impact characteristics, including cumulative impact profiles, and post-morbid outcomes in high school athletes. There appears to be no association between head impact biomechanics and post-concussive outcomes. As such, the use of biomechanical variables to predict injury severity does not appear feasible at this time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90455/1/neu-2E2011-2E1905.pd

Structure-activity relationships on cynnamoyl derivatives as inhibitors of p300 Histone acetyltransferase

Human p300 is a polyhedric transcriptional coactivator, playing a crucial role by acetylating histones on specific lysine residues. A great deal of evidences shows that p300 is involved in several diseases as leukemia, tumors and viral infection. Its involvement in pleiotropic biological roles and connections to diseases provide the rationale as to how its modulation could represent an amenable drug target. Several p300 inhibitors (HATi) have been described so far, but all suffer from low potency, lack of specificity or low cell-permeability, highlighting the need to find more effective inhibitors. Our cinnamoyl derivative, RC 56, was identified as active and selective p300 inhibitor, proving to be a good hit candidate to investigate the structure-activity relationship towards p300. Herein we describe the design, synthesis and biological evaluation of new HATi structurally related to our hit, investigating, moreover, the interactions between p300 and the best-emerged hits by means of induced fit docking and molecular dynamics simulations, gaining insight on the peculiar chemical features that influenced their activity toward the targeted enzyme

Cumulative Head Impact Burden in High School Football

Impacts to the head are common in collision sports such as football. Emerging research has begun to elucidate concussion tolerance levels, but sub-concussive impacts that do not result in clinical signs or symptoms of concussion are much more common, and are speculated to lead to alterations in cerebral structure and function later in life. We investigated the cumulative number of head impacts and their associated acceleration burden in 95 high school football players across four seasons of play using the Head Impact Telemetry System (HITS). The 4-year investigation resulted in 101,994 impacts collected across 190 practice sessions and 50 games. The number of impacts per 14-week season varied by playing position and starting status, with the average player sustaining 652 impacts. Linemen sustained the highest number of impacts per season (868); followed by tight ends, running backs, and linebackers (619); then quarterbacks (467); and receivers, cornerbacks, and safeties (372). Post-impact accelerations of the head also varied by playing position and starting status, with a seasonal linear acceleration burden of 16,746.1g, while the rotational acceleration and HIT severity profile burdens were 1,090,697.7-rad/sec2 and 10,021, respectively. The adolescent athletes in this study clearly sustained a large number of impacts to the head, with an impressive associated acceleration burden as a direct result of football participation. These findings raise concern about the relationship between sub-concussive head impacts incurred during football participation and late-life cerebral pathogenesis, and justify consideration of ways to best minimize impacts and mitigate cognitive declines.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90454/1/neu-2E2011-2E1825.pd