Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0

Immune Activation Reduces Sperm Quality in the Great Tit

Mounting an immune response against pathogens incurs costs to organisms by its effects on important life-history traits, such as reproductive investment and survival. As shown recently, immune activation produces large amounts of reactive species and is suggested to induce oxidative stress. Sperm are highly susceptible to oxidative stress, which can negatively impact sperm function and ultimately male fertilizing efficiency. Here we address the question as to whether mounting an immune response affects sperm quality through the damaging effects of oxidative stress. It has been demonstrated recently in birds that carotenoid-based ornaments can be reliable signals of a male's ability to protect sperm from oxidative damage. In a full-factorial design, we immune-challenged great tit males while simultaneously increasing their vitamin E availability, and assessed the effect on sperm quality and oxidative damage. We conducted this experiment in a natural population and tested the males' response to the experimental treatment in relation to their carotenoid-based breast coloration, a condition-dependent trait. Immune activation induced a steeper decline in sperm swimming velocity, thus highlighting the potential costs of an induced immune response on sperm competitive ability and fertilizing efficiency. We found sperm oxidative damage to be negatively correlated with sperm swimming velocity. However, blood resistance to a free-radical attack (a measure of somatic antioxidant capacity) as well as plasma and sperm levels of oxidative damage (lipid peroxidation) remained unaffected, thus suggesting that the observed effect did not arise through oxidative stress. Towards the end of their breeding cycle, swimming velocity of sperm of more intensely colored males was higher, which has important implications for the evolution of mate choice and multiple mating in females because females may accrue both direct and indirect benefits by mating with males having better quality sperm

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Initial Mutations Direct Alternative Pathways of Protein Evolution

Whether evolution is erratic due to random historical details, or is repeatedly directed along similar paths by certain constraints, remains unclear. Epistasis (i.e. non-additive interaction between mutations that affect fitness) is a mechanism that can contribute to both scenarios. Epistasis can constrain the type and order of selected mutations, but it can also make adaptive trajectories contingent upon the first random substitution. This effect is particularly strong under sign epistasis, when the sign of the fitness effects of a mutation depends on its genetic background. In the current study, we examine how epistatic interactions between mutations determine alternative evolutionary pathways, using in vitro evolution of the antibiotic resistance enzyme TEM-1 β-lactamase. First, we describe the diversity of adaptive pathways among replicate lines during evolution for resistance to a novel antibiotic (cefotaxime). Consistent with the prediction of epistatic constraints, most lines increased resistance by acquiring three mutations in a fixed order. However, a few lines deviated from this pattern. Next, to test whether negative interactions between alternative initial substitutions drive this divergence, alleles containing initial substitutions from the deviating lines were evolved under identical conditions. Indeed, these alternative initial substitutions consistently led to lower adaptive peaks, involving more and other substitutions than those observed in the common pathway. We found that a combination of decreased enzymatic activity and lower folding cooperativity underlies negative sign epistasis in the clash between key mutations in the common and deviating lines (Gly238Ser and Arg164Ser, respectively). Our results demonstrate that epistasis contributes to contingency in protein evolution by amplifying the selective consequences of random mutations

Prevalence of Epistasis in the Evolution of Influenza A Surface Proteins

The surface proteins of human influenza A viruses experience positive selection to escape both human immunity and, more recently, antiviral drug treatments. In bacteria and viruses, immune-escape and drug-resistant phenotypes often appear through a combination of several mutations that have epistatic effects on pathogen fitness. However, the extent and structure of epistasis in influenza viral proteins have not been systematically investigated. Here, we develop a novel statistical method to detect positive epistasis between pairs of sites in a protein, based on the observed temporal patterns of sequence evolution. The method rests on the simple idea that a substitution at one site should rapidly follow a substitution at another site if the sites are positively epistatic. We apply this method to the surface proteins hemagglutinin and neuraminidase of influenza A virus subtypes H3N2 and H1N1. Compared to a non-epistatic null distribution, we detect substantial amounts of epistasis and determine the identities of putatively epistatic pairs of sites. In particular, using sequence data alone, our method identifies epistatic interactions between specific sites in neuraminidase that have recently been demonstrated, in vitro, to confer resistance to the drug oseltamivir; these epistatic interactions are responsible for widespread drug resistance among H1N1 viruses circulating today. This experimental validation demonstrates the predictive power of our method to identify epistatic sites of importance for viral adaptation and public health. We conclude that epistasis plays a large role in shaping the molecular evolution of influenza viruses. In particular, sites with , which would normally not be identified as positively selected, can facilitate viral adaptation through epistatic interactions with their partner sites. The knowledge of specific interactions among sites in influenza proteins may help us to predict the course of antigenic evolution and, consequently, to select more appropriate vaccines and drugs

An action research approach to facilitating the adoption of a foot health assessment tool in India

Background: India has a diabetes population that is growing and alongside this, the incidence of limb threatening foot problems is increasing. Foot health care provision does not yet meet this demand. In one locality in India, clinicians had an unstructured approach to foot health assessments resulting in poor adoption of evidence based guidelines from the West and a persistence of serious foot complications. There was the perception that existing assessment tools did not take into account the local cultural, organizational and professional needs and there was a lack of ownership of any potential solution to the problem. Therefore, the aim of this work was to facilitate the ownership and development of a foot health assessment tool for use in the Indian context. In order to achieve this an action research approach was chosen. Methods: Participants were facilitated through the action and implementation phases of the action research cycle by the researchers. The action phase included generating a list of potential items for inclusion in the tool from a review of the literature to provide an evidence based foundation for the foot health assessment tool. A modified Delphi method was used to further refine the contents of the tool. Members of the Delphi Panel (n=8) were experts in their field of medicine and experts in delivering health care within services in India. Results: The outcome of the study was the adoption of a locally developed foot health assessment tool (Salford Indian Foot Health Assessment Tool, SIFT). It contains thirteen sections, which reflect the risk factors identified for assessing foot health agreed by the participants to fit the Indian context. The SIFT is supported with evidence based guidelines from the West and a training program was delivered by the researchers in order to support its implementation into clinical practice. Conclusion: An action research approach has facilitated the development and implementation of a locally created and owned foot health assessment tool. This in turn has resulted in the integration of evidence-based guidelines from the West with consideration to local cultural, organizational and professional needs and ultimately the needs of their patients. Further work is underway evaluating the outcomes of the SIFT in practice. Keywords: Diabetes; Action research; Foot health assessment

Measurement of the branching fraction ratios and CP asymmetries in B-→ D0 CP K-decays

We present a preliminary study of $B^- \to D^0_{CP} \pi^-$ and $B^- \to D^0_{CP} K^-$ decays, with the $D^0_{CP}$ reconstructed in the CP-odd eigenstates $K_s \pi^0$, $K_s \omega$, in the CP-even eigenstates $K^+ K^-$, $\pi^+ \pi^-$, and in the (non-CP) flavor eigenstate $K^\mp \pi^\pm$. Using a sample of about 382 million Y(4S) decays into BBbar pairs, collected with the BABAR detector operating at the PEP-II asymmetric-energy B Factory at SLAC, we measure the ratios of the branching fractions R_CP+- and the direct CP asymmetries A_CP+-. The results are: R_CP- = 0.81 \pm 0.10 (stat) \pm 0.05 (syst) R_CP+ = 1.07 \pm 0.10 (stat) \pm 0.04 (syst) A_CP- = -0.19 \pm 0.12 (stat) \pm 0.02 (syst) A_CP+ = 0.35 \pm 0.09 (stat) \pm 0.05 (syst