The Bobsled Push Start: Influence on Race Outcome and Push Athlete Talent Identification and Monitoring

Bobsled is an Olympic sport that has progressed from rudimentary in the 1800’s to highly technological replete with biomechanical analyses and investment in engineering from the world’s top engineers. Little to no investigation has been carried out on all the tracks and the interrelationship between various measures of starts and sled-travel down-track. Further, little quality research has been produced in the athletic characteristics required for high-level competition in bobsled. The present manuscript investigates the reliability of, and interrelationship between, start time, start velocity, split times, and finish times in World Cup 2- and 4-man bobsled competition. A strong relationship between the three variables is found, but further research is needed to elucidate the actual effects of the push start on the sled’s travel down-track because of several confounding variables. The present manuscript also investigates the tests commonly performed by the USA Bobsled and Skeleton federation as a means of talent identification and athlete monitoring. Strength and power tests may have more validity for discriminating between higher-level push athletes, so long as a sufficient threshold of running speed is present. Speed tests only discriminate well between lower level push athletes. Recommendations are made for modifying the current testing battery in such a way as to better identify talent and better monitor traveling athletes and informing coaching decisions about athlete preparedness for fast bobsled push starts

Cyclization of Peptide b9 Ions

The product ion mass spectra obtained by CID of the b9 ions derived by loss of neutral alanine from the MH+ ion of the peptides Tyr(Ala)9, (Ala)4Tyr(Ala)5, and (Ala)8TyrAla are essentially identical, indicative of full cyclization reaction to a common intermediate before fragmentation. This leads to abundant nondirect sequence ions in the product ion mass spectra of the b9 ions. The product ion mass spectra of the b8 ions from the first two peptides also are essentially identical. The fragmentation of the MH+ ions also leads to low intensity nondirect sequence ions in the product ion mass spectra. N-terminal acetylation blocks the cyclization and eliminates nondirect sequence fragment ions in the product ion mass spectra

Evaluating the Role of the Alzheimer’s Disease Risk Factor Pyk2 in Tau Phosphorylation, Pathology and Related Dysfunction

Alzheimer’s disease (AD), the most common cause of dementia, is the 6th leading cause of death in the US and the 5th leading cause of death in individuals 65 and older. As the global population ages, current projections suggest that AD may overwhelm existing healthcare infrastructure in the 21st century, with cases in the US expected to surpass 13.8 million by 2060. The need for additional disease modifying therapies is paramount, though the development of novel therapeutic strategies for the treatment of AD is limited by our current understanding of AD pathophysiology. The vast majority of AD cases are sporadic in nature, with age being the single greatest risk factor, however a growing list of genetic risk factors identified through recent genome wide association studies (GWAS) has the potential to reveal key insights into the molecular mechanisms that govern AD susceptibility and mediate disease progression. Given that AD is defined by the pathological processing of both Aβ and Tau, any evaluation of a specific AD risk factor must consider the role that gene-product plays with respect to both proteins. Our group has previously reported that the AD risk factor Pyk2 is required for Aβ synaptotoxicity as well as the presentation of Aβ-associated phenotypes in AD animal models. Although Pyk2 has been previously shown to regulate kinases known to phosphorylate Tau at pathophysiologically-relevant residues (e.g. GSK3β and Fyn), and while at least one group has reported direct phosphorylation of Tau by Pyk2 through over-expression experiments, direct evidence demonstrating Pyk2-dependent modulation of Tau phosphorylation through the manipulation of endogenous Pyk2 is lacking. Experiments described here show that both genetic deletion and pharmacological inhibition of Pyk2 increases the phosphorylation of Tau at a number of pathophysiologically-relevant residues. Furthermore, genetic deletion of Pyk2 in PS19 animals that over-express a mutant form of human Tau associated with frontotemporal dementia significantly reduces animal survivorship, impairs memory and augments synaptic C1q deposition. These results suggest that, while Pyk2 contributes to toxic Aβ signaling, Pyk2 conversely suppresses Tau phosphorylation and Tau-associated phenotypes. To explore the mechanism by which Pyk2 suppresses Tau phosphorylation, we conducted phospho-proteomics on hippocampal synaptosomes from WT and Pyk2-/- animals, revealing a number of proximate regulators of Tau modulated by Pyk2 expression. From this list of six kinases, we confirm that the activity of at least one hit, LKB1, is suppressed by basal levels of Pyk2 activity. We also show that the activity of a direct substrate of LKB1 and a known kinase of Tau, p38 MAPK, is also inhibited by Pyk2. Revealingly, the activities of LKB1 and p38 MAPK are highest in PS190/+;Pyk2-/- mice, suggesting that the activities of these two kinases may at least partially explain the increased Tau phosphorylation and exacerbated Tau-associated phenotypes observed in these animals. While the implications of these data preclude Pyk2 as a promising pharmacological target using conventional therapeutic approaches, these results, in conjunction with previous results from our group, uncover a complex role for Pyk2 at the intersection of Aβ and Tau

WOMID: A mentoring initiative for women working in international development aims to connect research and practice.

Balancing the early stages of a research career, while simultaneously keeping up to date with developments in the field generates some unique requirements for researchers in international development. WOMID is a new global mentoring initiative for women, facilitating mentorship between early career academics and practitioners. Alex Dorgan and Beth Harrison, who co-founded WOMID based on their own experiences of doing PhDs, explain what WOMID is all about and how you can get involved

Transitory interest-rate pegs under imperfect credibility

Housing construction, measured by housing starts, leads GDP in a number of countries. Measured as residential investment, the lead is observed only in the US and Canada; elsewhere, residential investment is coincident. Variants of existing theory, however, predict housing construction lagging GDP. In all countries in the sample, nominal interest rates are low ahead of GDP peaks. Introducing fully-amortizing mortgages and an estimated process for nominal interest rates into a standard model aligns the theory with the observations on starts; one-period loans are insufficient to generate the lead. Longer time to build then makes residential investment cyclically coinciden

Reactive collisions in quadrupole cells. 3: H/D exchange reactions of protonated aromatic amines with ND3

The H/D exchange reactions of a variety of protonated aromatic amines with ND3 in the collision cell of a hybrid BEqQ tandem mass spectrometer have been studied. The MH+ ions were prepared by CH4, i-C4H10, and NH3 chemical ionization (CI) and, for some amines, by fast-atom bombardment (FAB). Evidence is presented that the kinetic energy of the incident ion as well as its internal energy must be dissipated by nonexchanging collisions before exchange occurs; once deactivated the MH+ ions exchange efficiently, which leads, in most cases, to [MH]1 dx ions in which all active hydrogens have been exchanged. The MH1 ion of 1,3-phenylenediamine formed by gas-phase CI exchanges only very slightly with ND3 whereas a significant fraction of the MH+ ions formed by FAB exchange efficiently. This difference is rationalized in terms of dominant formation of the ring-protonated species in gas-phase CI reactions and significant formation of the N-protonated species by FAB with only the N-protonated species exchanging efficiently. Similar, although less pronounced, differences are observed for the MH+ ion of m-anisidine. In a number of cases apparent exchange of aromatic hydrogens also is observed. Evidence is presented for the interchange of ring and amine hydrogens in protonated aromatic amines and it is suggested that only the N-protonated species undergoes significant exchange with ND3